1427:
several reward functions. ... Rewards are attractive. They are motivating and make us exert an effort. ... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior. ... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward. ... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory) ... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses. The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning) ... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components. This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism's survival and reproduction, whereas all other components are only supportive of these functions. ... Rewards can also be intrinsic to behavior. They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards. ... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward. ... These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research and strongly support the learning and approach generating functions of reward.
1891:
2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a 'go' signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a 'brake' to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and
Nestler, 2011; Grueter et al., 2013). For example, optogenetic activation of NAc core and shell iMSNs suppressed the development of a cocaine CPP whereas selective ablation of NAc core and shell iMSNs ... enhanced the development and the persistence of an amphetamine CPP (Durieux et al., 2009; Lobo et al., 2010). These findings suggest that iMSNs can bidirectionally modulate drug reward. ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use.
5695:
causal implication of dopamine in musical pleasure, the authors have turned to directly manipulating dopaminergic signaling in the striatum, first by applying excitatory and inhibitory transcranial magnetic stimulation over their participants' left dorsolateral prefrontal cortex, a region known to modulate striatal function (5), and finally, in the current study, by administrating pharmaceutical agents able to alter dopamine synaptic availability (1), both of which influenced perceived pleasure, physiological measures of arousal, and the monetary value assigned to music in the predicted direction. ... While the question of the musical expression of emotion has a long history of investigation, including in PNAS (6), and the 1990s psychophysiological strand of research had already established that musical pleasure could activate the autonomic nervous system (7), the authors' demonstration of the implication of the reward system in musical emotions was taken as inaugural proof that these were veridical emotions whose study has full legitimacy to inform the neurobiology of our everyday cognitive, social, and affective functions (8). Incidentally, this line of work, culminating in the article by
Ferreri et al. (1), has plausibly done more to attract research funding for the field of music sciences than any other in this community. The evidence of Ferreri et al. (1) provides the latest support for a compelling neurobiological model in which musical pleasure arises from the interaction of ancient reward/valuation systems (striatal–limbic–paralimbic) with more phylogenetically advanced perception/predictions systems (temporofrontal).
3909:
bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."
4003:
cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. ... Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and
Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
1946:
regions, the NAc (described above) and the DS (described below) are most frequently examined with respect to addiction. Thus, only a brief description of the modulatory role of the basal ganglia in addiction-relevant circuits will be mentioned here. The overall output of the basal ganglia is predominantly via the thalamus, which then projects back to the PFC to form cortico-striatal-thalamo-cortical (CSTC) loops. Three CSTC loops are proposed to modulate executive function, action selection, and behavioral inhibition. In the dorsolateral prefrontal circuit, the basal ganglia primarily modulate the identification and selection of goals, including rewards.44 The OFC circuit modulates decision-making and impulsivity, and the anterior cingulate circuit modulates the assessment of consequences.44 These circuits are modulated by dopaminergic inputs from the VTA to ultimately guide behaviors relevant to addiction, including the persistence and narrowing of the behavioral repertoire toward drug seeking, and continued drug use despite negative consequences.43–45
2023:(components of which have been termed the extended amygdala, as discussed later in this chapter), hippocampus, hypothalamus, and frontal regions of cerebral cortex. These structures receive rich dopaminergic innervation from the ventral tegmental area (VTA) of the midbrain. Addictive drugs are rewarding and reinforcing because they act in brain reward pathways to enhance either dopamine release or the effects of dopamine in the NAc or related structures, or because they produce effects similar to dopamine. ... A macrostructure postulated to integrate many of the functions of this circuit is described by some investigators as the extended amygdala. The extended amygdala is said to comprise several basal forebrain structures that share similar morphology, immunocytochemical features, and connectivity and that are well suited to mediating aspects of reward function; these include the bed nucleus of the stria terminalis, the central medial amygdala, the shell of the NAc, and the sublenticular substantia innominata.
5629:
responses elicited by music. In particular, we found that risperidone impaired participants' ability to experience musical pleasure, whereas levodopa enhanced it. ... Here, in contrast, studying responses to abstract rewards in human subjects, we show that manipulation of dopaminergic transmission affects both the pleasure (i.e., amount of time reporting chills and emotional arousal measured by EDA) and the motivational components of musical reward (money willing to spend). These findings suggest that dopaminergic signaling is a sine qua non condition not only for motivational responses, as has been shown with primary and secondary rewards, but also for hedonic reactions to music. This result supports recent findings showing that dopamine also mediates the perceived pleasantness attained by other types of abstract rewards and challenges previous findings in animal models on primary rewards, such as food.
3948:
drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
3845:ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a
1262:) has objective features and was essentially the same across various animal species. Most neuroscience studies have shown that the more dopamine released by the reward, the more effective the reward is. This is called the hedonic impact, which can be changed by the effort for the reward and the reward itself. Berridge discovered that blocking dopamine systems did not seem to change the positive reaction to something sweet (as measured by facial expression). In other words, the hedonic impact did not change based on the amount of sugar. This discounted the conventional assumption that dopamine mediates pleasure. Even with more-intense dopamine alterations, the data seemed to remain constant. However, a clinical study from January 2019 that assessed the effect of a dopamine precursor (
2975:
can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. ... Associative learning and prediction are important contributors to motivation for rewards. Learning gives incentive value to arbitrary cues such as a
Pavlovian conditioned stimulus (CS) that is associated with a reward (unconditioned stimulus or UCS). Learned cues for reward are often potent triggers of desires. For example, learned cues can trigger normal appetites in everyone, and can sometimes trigger compulsive urges and relapse in addicts.
1212:. Pavlov used the reward system by rewarding dogs with food after they had heard a bell or another stimulus. Pavlov was rewarding the dogs so that the dogs associated food, the reward, with the bell, the stimulus. Edward L. Thorndike used the reward system to study operant conditioning. He began by putting cats in a puzzle box and placing food outside of the box so that the cat wanted to escape. The cats worked to get out of the puzzle box to get to the food. Although the cats ate the food after they escaped the box, Thorndike learned that the cats attempted to escape the box without the reward of food. Thorndike used the rewards of food and freedom to stimulate the reward system of the cats. Thorndike used this to see how the cats learned to escape the box. More recently,
798:
According to
Robinson and Berridge, wanting and liking are two aspects of the same process, so rewards are usually wanted and liked to the same degree. However, wanting and liking also change independently under certain circumstances. For example, rats that do not eat after receiving dopamine (experiencing a loss of desire for food) act as though they still like food. In another example, activated self-stimulation electrodes in the lateral hypothalamus of rats increase appetite, but also cause more adverse reactions to tastes such as sugar and salt; apparently, the stimulation increases wanting but not liking. Such results demonstrate that the reward system of rats includes independent processes of wanting and liking. The wanting component is thought to be controlled by
1574:(Georgiadis et al., 2012; Kringelbach, 2005; Kringelbach et al., 2003; Small et al., 2001; Veldhuizen et al., 2010). Finally, in the brainstem, a hindbrain site near the parabrachial nucleus of dorsal pons also appears able to contribute to hedonic gains of function (Söderpalm and Berridge, 2000). A brainstem mechanism for pleasure may seem more surprising than forebrain hot spots to anyone who views the brainstem as merely reflexive, but the pontine parabrachial nucleus contributes to taste, pain, and many visceral sensations from the body and has also been suggested to play an important role in motivation (Wu et al., 2012) and in human emotion (especially related to the somatic marker hypothesis) (Damasio, 2010).
3013:
terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
5111:, p. 215b,"As such it is surprising that behavioral studies have suggested that reinforcement learning is intact in schizophrenia when learning is relatively implicit (though, see Siegert et al., 2008 for evidence of impaired Serial Reaction Time task learning), but more impaired when explicit representations of stimulus-reward contingencies are needed (see Gold et al., 2008). This pattern has given rise to the theory that the striatally mediated gradual reinforcement learning system may be intact in schizophrenia, while more rapid, on-line, cortically mediated learning systems are impaired."
811:
multiple parts of the amygdala (the bed nucleus of the stria terminalis, the central nucleus), the
Nucleus Accumbens, and signal molecules including norepinephrine, corticotropin-releasing factor, and dynorphin. This circuit is also hypothesized to mediate the unpleasant components of stress, and is thus thought to be involved in addiction and withdrawal. While the reward circuit mediates the initial positive reinforcement involved in the development of addiction, it is the anti-reward circuit that later dominates via negative reinforcement that motivates the pursuit of the rewarding stimuli.
1186:. Typically, rats will press a lever hundreds or thousands of times per hour to obtain this brain stimulation, stopping only when they are exhausted. While trying to teach rats how to solve problems and run mazes, stimulation of certain regions of the brain where the stimulation was found seemed to give pleasure to the animals. They tried the same thing with humans and the results were similar. The explanation to why animals engage in a behavior that has no value to the survival of either themselves or their species is that the brain stimulation is activating the system underlying reward.
1038:. Rats also learn to lever-press for cocaine injections into the medial prefrontal cortex, which works by increasing dopamine turnover in the nucleus accumbens. Nicotine infused directly into the nucleus accumbens also enhances local dopamine release, presumably by a presynaptic action on the dopaminergic terminals of this region. Nicotinic receptors localize to dopaminergic cell bodies and local nicotine injections increase dopaminergic cell firing that is critical for nicotinic reward. Some additional habit-forming drugs are also likely to decrease the output of
606:(the Nucleus Accumbens) is broadly involved in acquiring behavior when fed into by the VTA, and eliciting behavior when fed into by the PFC. The NAc shell projects to the pallidum and the VTA, regulating limbic and autonomic functions. This modulates the reinforcing properties of stimuli, and short term aspects of reward. The NAc Core projects to the substantia nigra and is involved in the development of reward-seeking behaviors and its expression. It is involved in spatial learning, conditional response, and impulsive choice; the long term elements of reward.
1130:. The experience of "liking" is frequently reported to be intact, both behaviorally and neurally, although results may be specific to certain stimuli, such as monetary rewards. Furthermore, implicit learning and simple reward-related tasks are also intact in schizophrenia. Rather, deficits in the reward system are apparent during reward-related tasks that are cognitively complex. These deficits are associated with both abnormal striatal and OFC activity, as well as abnormalities in regions associated with cognitive functions such as the
136:; however, the converse statement also holds true: positive reinforcers are rewarding.The reward system motivates animals to approach stimuli or engage in behaviour that increases fitness (sex, energy-dense foods, etc.). Survival for most animal species depends upon maximizing contact with beneficial stimuli and minimizing contact with harmful stimuli. Reward cognition serves to increase the likelihood of survival and reproduction by causing associative learning, eliciting approach and consummatory behavior, and triggering
850:. This distinction is thought to reflect two forms of learning, model free and model based. Model free learning involves the simple caching and updating of values. In contrast, model based learning involves the storage and construction of an internal model of events that allows inference and flexible prediction. Although pavlovian conditioning is generally assumed to be model-free, the incentive salience assigned to a conditioned stimulus is flexible with regard to changes in internal motivational states.
790:(i.e., incentive salience) towards rewarding stimuli, but also for aversive motivational salience, which directs behavior away from undesirable stimuli. In the dorsal striatum, activation of D1 expressing MSNs produces appetitive incentive salience, while activation of D2 expressing MSNs produces aversion. In the NAcc, such a dichotomy is not as clear cut, and activation of both D1 and D2 MSNs is sufficient to enhance motivation, likely via disinhibiting the VTA through inhibiting the ventral pallidum.
67:
3849:(34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
5123:, p. 216, "We have recently shown that individuals with schizophrenia can show improved cognitive control performance when information about rewards are externally presented but not when they must be internally maintained (Mann et al., 2013), with some evidence for impairments in DLPFC and striatal activation during internal maintenance of reward information being associated with individuals' differences in motivation (Chung and Barch, 2016)."
47:
544:
1170:
5099:, p. 215a,"Several recent reviews (e.g., Cohen and Minor, 2010) have found that individuals with schizophrenia show relatively intact self-reported emotional responses to affect-eliciting stimuli as well as other indicators of intact response...A more mixed picture arises from functional neuroimaging studies examining brain responses to other types of pleasurable stimuli in schizophrenia (Paradiso et al., 2003)"
38:
6484:
508:, ventral hippocampus, and medial prefrontal cortex can drive incentive salience. Furthermore, while most studies find that NAcc neurons reduce firing in response to reward, a number of studies find the opposite response. This had led to the proposal of the disinhibition (or depolarization) hypothesis, that proposes that excitation or NAcc neurons, or at least certain subsets, drives reward related behavior.
1069:, traditionally defined as a reduced capacity to feel pleasure, has been re-examined as reflecting blunted incentive salience, as most anhedonic populations exhibit intact "liking". On the other end of the spectrum, heightened incentive salience that is narrowed for specific stimuli is characteristic of behavioral and drug addictions. In the case of fear or paranoia, dysfunction may lie in elevated
523:. There are several explanations as to why the mesolimbic dopamine pathway is central to circuits mediating reward. First, there is a marked increase in dopamine release from the mesolimbic pathway when animals engage in intracranial self-stimulation. Second, experiments consistently indicate that brain-stimulation reward stimulates the reinforcement of pathways that are normally activated by
6522:
163:) rewards. Intrinsic rewards are unconditioned rewards that are attractive and motivate behavior because they are inherently pleasurable. Extrinsic rewards (e.g., money or seeing one's favorite sports team winning a game) are conditioned rewards that are attractive and motivate behavior but are not inherently pleasurable. Extrinsic rewards derive their motivational value as a result of a
1086:
probing dopamine function in depression have reported inconsistent results. Although postmortem and neuroimaging studies have found abnormalities in numerous regions of the reward system, few findings are consistently replicated. Some studies have reported reduced NAcc, hippocampus, medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC) activity, as well as elevated
907:. Alone NMDA mediated activation of ERK is self-limited, as NMDA activation also inhibits PKA mediated inhibition of ERK deactivating phosphatases. However, when D1 and NMDA cascades are co-activated, they work synergistically, and the resultant activation of ERK regulates synaptic plasticity in the form of spine restructuring, transport of AMPA receptors, regulation of
1103:
social interactions, and increased immobility in the forced swim test. CMS similarly reduces sucrose preference, and behavioral despair as assessed by tail suspension and forced swim tests. Animals susceptible to CSDS exhibit increased phasic VTA firing, and inhibition of VTA-NAcc projections attenuates behavioral deficits induced by CSDS. However, inhibition of VTA-
58:
1146:, core aspects of the reward system are underactive, making it challenging to derive reward from regular activities. Those with the disorder experience a boost of motivation after a high-stimulation behaviour triggers a release of dopamine. In the aftermath of that boost and reward, the return to baseline levels results in an immediate drop in motivation.
763:
128:). Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In
2917: On the other hand, intense euphoria is harder to come by than everyday pleasures. The reason may be that strong enhancement of pleasure – like the chemically induced pleasure bump we produced in lab animals – seems to require activation of the entire network at once. Defection of any single component dampens the high.
716:. The hotspot within the nucleus accumbens shell is located in the rostrodorsal quadrant of the medial shell, while the hedonic coldspot is located in a more posterior region. The posterior ventral pallidum also contains a hedonic hotspot, while the anterior ventral pallidum contains a hedonic coldspot. In rats, microinjections of
6510:
837:. In classical conditioning, a reward can act as an unconditioned stimulus that, when associated with the conditioned stimulus, causes the conditioned stimulus to elicit both musculoskeletal (in the form of simple approach and avoidance behaviors) and vegetative responses. In operant conditioning, a reward may act as a
2984:
incentive salience are often visible that can be used in neuroscience experiments: (i) UCS-directed 'wanting' – CS-triggered pulses of intensified 'wanting' for the UCS reward; and (ii) CS-directed 'wanting' – motivated attraction to the
Pavlovian cue, which makes the arbitrary CS stimulus into a motivational magnet.
4099:ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the
3947:
For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other
3908:
et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also
1890:
receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and
Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al.,
1573:
reactions elicited by sweetness, similar to the NAc and VP hot spots. Successful confirmation of hedonic hot spots in the OFC or insula would be important and possibly relevant to the orbitofrontal mid-anterior site mentioned earlier that especially tracks the subjective pleasure of foods in humans
1085:
Certain types of depression are associated with reduced motivation, as assessed by willingness to expend effort for reward. These abnormalities have been tentatively linked to reduced activity in areas of the striatum, and while dopaminergic abnormalities are hypothesized to play a role, most studies
617:
in stimulus-response learning foundational to
Pavlovian response. On repeated activation by a stimuli, the Nucleus Accumbens can activate the Dorsal Striatum via an intrastriatal loop. The transition of signals from the NAc to the DS allows reward associated cues to activate the DS without the reward
5084:
They also provide a separate assessment of the consummatory anhedonia (reduced experience of pleasure derived from ongoing enjoyable activities) and anticipatory anhedonia (reduced ability to anticipate future pleasure). In fact, the former one seems to be relatively intact in schizophrenia, whereas
1426:
Rewards in operant conditioning are positive reinforcers. ... Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of
766:
Tuning of appetitive and defensive reactions in the nucleus accumbens shell (above). AMPA blockade requires D1 function in order to produce motivated behaviors, regardless of valence, and D2 function to produce defensive behaviors. GABA agonism, on the other hand, does not requires dopamine receptor
728:
are capable of enhancing liking reactions in these hotspots. The hedonic hotspots located in the anterior OFC and posterior insula have been demonstrated to respond to orexin and opioids in rats, as has the overlapping hedonic coldspot in the anterior insula and posterior OFC. On the other hand, the
5694:
In a pharmacological study published in PNAS, Ferreri et al. (1) present evidence that enhancing or inhibiting dopamine signaling using levodopa or risperidone modulates the pleasure experienced while listening to music. ... In a final salvo to establish not only the correlational but also the
4002:
Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. ... Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and
2974:
Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes
Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that
1177:
The first clue to the presence of a reward system in the brain came with an accidental discovery by James Olds and Peter Milner in 1954. They discovered that rats would perform behaviors such as pressing a bar, to administer a brief burst of electrical stimulation to specific sites in their brains.
1094:
activity during tasks related to reward or positive stimuli. These neuroimaging abnormalities are complemented by little post mortem research, but what little research has been done suggests reduced excitatory synapses in the mPFC. Reduced activity in the mPFC during reward related tasks appears to
1025:
has been the most-frequently-studied brain-stimulation reward site, particularly in studies of the effects of drugs on brain stimulation reward. The neurotransmitter system that has been most-clearly identified with the habit-forming actions of drugs-of-abuse is the mesolimbic dopamine system, with
438:
through their projections to the ventral tegmental area (VTA). The LDT and PPTg both send glutaminergic projections to the VTA that synapse on dopaminergic neurons, both of which can produce incentive salience. The LHb sends glutaminergic projections, the majority of which synapse on GABAergic RMTg
5628:
Listening to pleasurable music is often accompanied by measurable bodily reactions such as goose bumps or shivers down the spine, commonly called 'chills' or 'frissons.' ... Overall, our results straightforwardly revealed that pharmacological interventions bidirectionally modulated the reward
3015:
The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is
1990:
Studies have shown that cravings are underpinned by activation of the reward and motivation circuits (McBride et al., 2006, Wang et al., 2007, Wing et al., 2012, Goldman et al., 2013, Jansen et al., 2013 and Volkow et al., 2013). According to these authors, the main neural structures involved are:
1568:
In the prefrontal cortex, recent evidence indicates that the OFC and insula cortex may each contain their own additional hot spots (D.C. Castro et al., Soc. Neurosci., abstract). In specific subregions of each area, either opioid-stimulating or orexin-stimulating microinjections appear to enhance
1299:
aspect of rewards. It explains the compulsive use of drugs by drug addicts even when the drug no longer produces euphoria, and the cravings experienced even after the individual has finished going through withdrawal. Some addicts respond to certain stimuli involving neural changes caused by drugs.
1102:
Attempts to investigate underlying neural circuitry in animal models has also yielded conflicting results. Two paradigms are commonly used to simulate depression, chronic social defeat (CSDS), and chronic mild stress (CMS), although many exist. CSDS produces reduced preference for sucrose, reduced
797:
contains separable psychological components: wanting (incentive) and liking (pleasure). To explain increasing contact with a certain stimulus such as chocolate, there are two independent factors at work – our desire to have the chocolate (wanting) and the pleasure effect of the chocolate (liking).
209:
Terms that are commonly used to describe behavior related to the "wanting" or desire component of reward include appetitive behavior, approach behavior, preparatory behavior, instrumental behavior, anticipatory behavior, and seeking. Terms that are commonly used to describe behavior related to the
4681:
In a relatively recent literature, studies of motivation and reinforcement in depression have been largely consistent in detecting differences as compared to healthy controls (Whitton et al. 2015). In several studies using the effort expenditure for reward task (EEfRT), patients with MDD expended
1945:
Regions of the basal ganglia, which include the dorsal and ventral striatum, internal and external segments of the globus pallidus, subthalamic nucleus, and dopaminergic cell bodies in the substantia nigra, are highly implicated not only in fine motor control but also in PFC function.43 Of these
3012:
VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse
2914:
So it makes sense that the real pleasure centers in the brain – those directly responsible for generating pleasurable sensations – turn out to lie within some of the structures previously identified as part of the reward circuit. One of these so-called hedonic hotspots lies in a subregion of the
1193:
and Peter Milner found that low-voltage electrical stimulation of certain regions of the brain of the rat acted as a reward in teaching the animals to run mazes and solve problems. It seemed that stimulation of those parts of the brain gave the animals pleasure, and in later work humans reported
810:
Koobs & Le Moal proposed that there exists a separate circuit responsible for the attenuation of reward-pursuing behavior, which they termed the anti-reward circuit. This component acts as brakes on the reward circuit, thus preventing the over pursuit of food, sex, etc. This circuit involves
632:
Notably, abstinence from addicting drugs activates the PFC, glutamatergic projection to the NAc, which leads to strong cravings, and modulates reinstatement of addiction behaviors resulting from abstinence. The PFC also interacts with the VTA through the mesocortical pathway, and helps associate
3555:
Importantly, we found evidence of increased activity in the direct pathway; both intracellular changes in the expression of the plasticity marker pERK and AMPA/NMDA ratios evoked by stimulating cortical afferents were increased in the D1-direct pathway neurons. In contrast, D2 neurons showed an
3018:
The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of
3071:
For instance, mesolimbic dopamine, probably the most popular brain neurotransmitter candidate for pleasure two decades ago, turns out not to cause pleasure or liking at all. Rather dopamine more selectively mediates a motivational process of incentive salience, which is a mechanism for wanting
2983:
When a Pavlovian CS+ is attributed with incentive salience it not only triggers 'wanting' for its UCS, but often the cue itself becomes highly attractive – even to an irrational degree. This cue attraction is another signature feature of incentive salience ... Two recognizable features of
1107:
projections exacerbates social withdrawal. On the other hand, CMS associated reductions in sucrose preference and immobility were attenuated and exacerbated by VTA excitation and inhibition, respectively. Although these differences may be attributable to different stimulation protocols or poor
492:
Two theories exist with regard to the activity of the nucleus accumbens and the generation liking and wanting. The inhibition (or hyperpolarization) hypothesis proposes that the nucleus accumbens exerts tonic inhibitory effects on downstream structures such as the ventral pallidum,
3840:
The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its
1076:
Neuroimaging studies across diagnoses associated with anhedonia have reported reduced activity in the OFC and ventral striatum. One meta analysis reported anhedonia was associated with reduced neural response to reward anticipation in the caudate nucleus, putamen, nucleus accumbens and medial
2022:
The neural substrates that underlie the perception of reward and the phenomenon of positive reinforcement are a set of interconnected forebrain structures called brain reward pathways; these include the nucleus accumbens (NAc; the major component of the ventral striatum), the basal forebrain
1114:
stimulation of the mPFC as a whole produces antidepressant effects. This effect appears localized to the rodent homologue of the pgACC (the prelimbic cortex), as stimulation of the rodent homologue of the sgACC (the infralimbic cortex) produces no behavioral effects. Furthermore, deep brain
3019:
motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.
841:
in that it increases or supports actions that lead to itself. Learned behaviors may or may not be sensitive to the value of the outcomes they lead to; behaviors that are sensitive to the contingency of an outcome on the performance of an action as well as the outcome value are
439:
neurons that in turn drive inhibition of dopaminergic VTA neurons, although some LHb projections terminate on VTA interneurons. These LHb projections are activated both by aversive stimuli and by the absence of an expected reward, and excitation of the LHb can induce aversion.
5211:
Blum, Kenneth; Chen, Amanda Lih-Chuan; Braverman, Eric R; Comings, David E; Chen, Thomas JH; Arcuri, Vanessa; Blum, Seth H; Downs, Bernard W; Waite, Roger L; Notaro, Alison; Lubar, Joel; Williams, Lonna; Prihoda, Thomas J; Palomo, Tomas; Oscar-Berman, Marlene (October 2008).
853:
Distinct neural systems are responsible for learning associations between stimuli and outcomes, actions and outcomes, and stimuli and responses. Although classical conditioning is not limited to the reward system, the enhancement of instrumental performance by stimuli (i.e.,
744:. Furthermore, inhibition of one hotspot results in the blunting of the effects of activating another hotspot. Therefore, the simultaneous activation of every hedonic hotspot within the reward system is believed to be necessary for generating the sensation of an intense
598:
The striatum is broadly involved in acquiring and eliciting learned behaviors in response to a rewarding cue. The VTA projects to the striatum, and activates the GABA-ergic Medium Spiny Neurons via D1 and D2 receptors within the ventral (Nucleus Accumbens) and dorsal
535:. Third, when animals are administered addictive drugs or engage in naturally rewarding behaviors, such as feeding or sexual activity, there is a marked release of dopamine within the nucleus accumbens. However, dopamine is not the only reward compound in the brain.
1050:
to the mesolimbic dopamine neurons (primary substrate of opiate reward), the mesolimbic dopamine neurons themselves (primary substrate of psychomotor stimulant reward), and GABAergic efferents to the mesolimbic dopamine neurons (a secondary site of opiate reward).
1115:
stimulation in the infralimbic cortex, which is thought to have an inhibitory effect, also produces an antidepressant effect. This finding is congruent with the observation that pharmacological inhibition of the infralimbic cortex attenuates depressive behaviors.
643:
The Hippocampus has multiple functions, including in the creation and storage of memories . In the reward circuit, it serves to contextual memories and associated cues. It ultimately underpins the reinstatement of reward-seeking behaviors via cues, and contextual
3084:
Calipari, Erin S.; Bagot, Rosemary C.; Purushothaman, Immanuel; Davidson, Thomas J.; Yorgason, Jordan T.; Peña, Catherine J.; Walker, Deena M.; Pirpinias, Stephen T.; Guise, Kevin G.; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J. (8 March 2016).
785:
Activation of the dorsorostral region of the nucleus accumbens correlates with increases in wanting without concurrent increases in liking. However, dopaminergic neurotransmission into the nucleus accumbens shell is responsible not only for appetitive
628:
The VTA dopaminergic neurons project to the PFC, activating glutaminergic neurons that project to multiple other regions, including the Dorsal Striatum and NAc, ultimately allowing the PFC to mediate salience and conditional behaviors in response to
2845:
Here, we show that opioid or orexin stimulations in orbitofrontal cortex and insula causally enhance hedonic "liking" reactions to sweetness and find a third cortical site where the same neurochemical stimulations reduce positive hedonic
476:
are components of the reward system as well. The glutamatergic projection nuclei in the subthalamic nucleus, prefrontal cortex, hippocampus, thalamus, and amygdala connect to other parts of the reward system via glutamate pathways. The
767:
function (below). The expansion of the anatomical regions that produce defensive behaviors under stress, and appetitive behaviors in the home environment produced by AMPA antagonism. This flexibility is less evident with GABA agonism.
2760:
Kutlu, M. G., & Gould, T. J. (2016). Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction. Learning & memory, 23(10),
3400:
Koob G. F., Le Moal M. (2008). Addiction and the brain antireward system. Annu. Rev. Psychol. 59 29–53. 10.1146/annurev.psych.59.103006.093548 Koob G. F., Sanna P. P., Bloom F. E. (1998). Neuroscience of addiction. Neuron 21
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Koob G. F., Le Moal M. (2008). Addiction and the brain antireward system. Annu. Rev. Psychol. 59 29–53. 10.1146/annurev.psych.59.103006.093548 Koob G. F., Sanna P. P., Bloom F. E. (1998). Neuroscience of addiction. Neuron 21
895:, respectively. These changes in synaptic plasticity and the accompanying learning is dependent upon activation of striatal D1 and NMDA receptors. The intracellular cascade activated by D1 receptors involves the recruitment of
4015:
Beloate LN, Weems PW, Casey GR, Webb IC, Coolen LM (February 2016). "Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats".
2736:
Yin, H. H., Knowlton, B. J., & Balleine, B. W. (2005). Blockade of NMDA receptors in the dorsomedial striatum prevents action–outcome learning in instrumental conditioning. European Journal of Neuroscience, 22(2),
2189:
Caligiore D, Pezzulo G, Baldassarre G, Bostan AC, Strick PL, Doya K, Helmich RC, Dirkx M, Houk J, Jörntell H, Lago-Rodriguez A, Galea JM, Miall RC, Popa T, Kishore A, Verschure PF, Zucca R, Herreros I (February 2017).
672:
is a component of reward, but not all rewards are pleasurable (e.g., money does not elicit pleasure unless this response is conditioned). Stimuli that are naturally pleasurable, and therefore attractive, are known as
2915:
nucleus accumbens called the medial shell. A second is found within the ventral pallidum, a deep-seated structure near the base of the forebrain that receives most of its signals from the nucleus accumbens. ...
2859:
515:. Regions include the lateral hypothalamus and medial forebrain bundles, which are especially effective. Stimulation there activates fibers that form the ascending pathways; the ascending pathways include the
5706:
Young, Jared W.; Anticevic, Alan; Barch, Deanna M. (2018). "Cognitive and Motivational Neuroscience of Psychotic Disorders". In Charney, Dennis S.; Sklar, Pamela; Buxbaum, Joseph D.; Nestler, Eric J. (eds.).
561:(VTA) is important in responding to stimuli and cues that indicate a reward is present. Rewarding stimuli (and all addictive drugs) act on the circuit by triggering the VTA to release dopamine signals to the
2708:
Kokane, S. S., & Perrotti, L. I. (2020). Sex Differences and the Role of Estradiol in Mesolimbic Reward Circuits and Vulnerability to Cocaine and Opiate Addiction. Frontiers in Behavioral Neuroscience,
1046:, a secondary site of opiate-rewarding actions on medium spiny output neurons of the nucleus accumbens. Thus the following form the core of currently characterised drug-reward circuitry; GABAergic
4405:
Westfall, Thomas C.; Grant, Heather; Perry, Holly (January 1983). "Release of dopamine and 5-hydroxytryptamine from rat striatal slices following activation of nicotinic cholinergic receptors".
1960:"The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations"
696:– i.e., brain structures that mediate pleasure or "liking" reactions from intrinsic rewards. As of October 2017, hedonic hotspots have been identified in subcompartments within the
5162:"New perspectives on catecholaminergic regulation of executive circuits: evidence for independent modulation of prefrontal functions by midbrain dopaminergic and noradrenergic neurons"
2979:
A brief CS encounter (or brief UCS encounter) often primes a pulse of elevated motivation to obtain and consume more reward UCS. This is a signature feature of incentive salience.
658:, and likely underpins the creation of strong cue-associated memories. It also is important in mediating the anxiety effects of withdrawal, and increased drug intake in addiction.
4665:
Treadway, Michael, T. (2016). "The Neurobiology of Motivational Deficits in Depression— An Update on Candidate Pathomechanisms". In Simpson, Eleanor H.; Balsam, Peter D. (eds.).
6222:
5336:
5331:
2476:
You ZB, Chen YQ, Wise RA (2001). "Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation".
5578:
Ferreri L, Mas-Herrero E, Zatorre RJ, Ripollés P, Gomez-Andres A, Alicart H, Olivé G, Marco-Pallarés J, Antonijoan RM, Valle M, Riba J, Rodriguez-Fornells A (January 2019).
3568:
Nakanishi, S; Hikida, T; Yawata, S (12 December 2014). "Distinct dopaminergic control of the direct and indirect pathways in reward-based and avoidance learning behaviors".
685:
with an intrinsic reward. In other words, extrinsic rewards function as motivational magnets that elicit "wanting", but not "liking" reactions once they have been acquired.
3072:
rewards but not for liking them .... Rather opioid stimulation has the special capacity to enhance liking only if the stimulation occurs within an anatomical hotspot
531:
or intracranial self-stimulation can exert more powerful activation of central reward mechanisms because they activate the reward center directly rather than through the
5509:
4694:
2898:
1042:
as a consequence, despite activating dopaminergic projections. For opiates, the lowest-threshold site for reward effects involves actions on GABAergic neurons in the
3521:
Balleine, BW; Morris, RW; Leung, BK (2 December 2015). "Thalamocortical integration of instrumental learning and performance and their disintegration in addiction".
4329:
Goeders N.E., Smith J.E. (1993). "Intracranial cocaine self-administration into the medial prefrontal cortex increases dopamine turnover in the nucleus accumbens".
2770:
McGaugh, J. L. (July 2004). "The amygdala modulates the consolidation of memories of emotionally arousing experiences". Annual Review of Neuroscience. 27 (1): 1–28.
2239:
Ogawa, SK; Watabe-Uchida, M (2018). "Organization of dopamine and serotonin system: Anatomical and functional mapping of monosynaptic inputs using rabies virus".
1991:
the nucleus accumbens, dorsal striatum, orbitofrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), amygdala, hippocampus and insula.
1278:
as well as subjective ratings – found that the manipulation of dopamine neurotransmission bidirectionally regulates pleasure cognition (specifically, the
167:(i.e., conditioning) with intrinsic rewards. Extrinsic rewards may also elicit pleasure (e.g., euphoria from winning a lot of money in a lottery) after being
6242:
3193:
Soares-Cunha, Carina; Coimbra, Barbara; Sousa, Nuno; Rodrigues, Ana J. (September 2016). "Reappraising striatal D1- and D2-neurons in reward and aversion".
5384:
3295:
Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J. (September 2016).
892:
258:
144:, certain substances over-activate the reward circuit, leading to compulsive substance-seeking behavior resulting from synaptic plasticity in the circuit.
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itself being present. This can activate cravings and reward-seeking behaviors (and is responsible for triggering relapse during abstinence in addiction).
179:
In neuroscience, the reward system is a collection of brain structures and neural pathways that are responsible for reward-related cognition, including
2718:
Becker, J. B., & Chartoff, E. (2019). Sex differences in neural mechanisms mediating reward and addiction. Neuropsychopharmacology, 44(1), 166-183.
453:
to communicate with other neurons) that project out of the ventral tegmental area are part of the reward system; in these pathways, dopamine acts on
1308:
reactions occur. Human and animal brains and behaviors experience similar changes regarding reward systems because these systems are so prominent.
2524:"Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry"
2727:
Stoof, J. C., & Kebabian, J. W. (1984). Two dopamine receptors: biochemistry, physiology and pharmacology. Life sciences, 35(23), 2281-2296.
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where they could stimulate the reward system by pressing a lever, the rats pressed for hours. Research in the next two decades established that
874:
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4254:
3005:
2015:
988:
protein tails (i.e., histone modifications) in specific regions of the brain are also known to play a crucial role in the molecular basis of
1258:, and these expressions were similarly displayed by human newborns, orangutans, and rats. This was evidence that pleasure (specifically,
1202:
is one of the main chemicals aiding neural signaling in these regions, and dopamine was suggested to be the brain's "pleasure chemical".
6435:
5907:
5764:
732:
Hedonic hotspots are functionally linked, in that activation of one hotspot results in the recruitment of the others, as indexed by the
585:
265:
portion of the loop drives activity within the reward system. Most of the pathways that connect structures within the reward system are
6297:
3929:
Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T (2012). "Epigenetic regulation in drug addiction".
3352:
Soares-Cunha, Carina; Coimbra, Bárbara; Domingues, Ana Verónica; Vasconcelos, Nivaldo; Sousa, Nuno; Rodrigues, Ana João (March 2018).
511:
After nearly 50 years of research on brain-stimulation reward, experts have certified that dozens of sites in the brain will maintain
3841:
subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. ...
2919: Whether the pleasure circuit – and in particular, the ventral pallidum – works the same way in humans is unclear.
5716:
4211:
4140:
4103:
gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is
2751:
Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: a neurocircuitry analysis. The Lancet Psychiatry, 3(8), 760-773.
1669:
5361:
2192:"Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex"
1034:. The reward-relevant actions of amphetamine and cocaine are in the dopaminergic synapses of the nucleus accumbens and perhaps the
3904:
Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (
6552:
6360:
6227:
774:
is the "wanting" or "desire" attribute, which includes a motivational component, that is assigned to a rewarding stimulus by the
1704:
1586:
Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan (14 December 2016).
6547:
6440:
6430:
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opposing change in plasticity; stimulation of cortical afferents reduced AMPA/NMDA ratios on those neurons (Shan et al., 2014).
855:
3425:"Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks"
6562:
5134:
1131:
427:
415:
1073:. In modern literature, anhedonia is associated with the proposed two forms of pleasure, "anticipatory" and "consummatory".
1588:"Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum"
6063:
1734:
Duarte, Isabel C.; Afonso, Sónia; Jorge, Helena; Cayolla, Ricardo; Ferreira, Carlos; Castelo-Branco, Miguel (1 May 2017).
1179:
512:
6500:
6292:
6277:
6265:
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Morales, M; Margolis, EB (February 2017). "Ventral tegmental area: cellular heterogeneity, connectivity and behaviour".
903:, the inhibition of phosphatases that deactivate ERK. NMDA receptors activate ERK through a different but interrelated
504:
are capable of eliciting both "liking" and "wanting" reactions in the nucleus accumbens, glutaminergic inputs from the
5890:
5450:
Fridlund, Alan and James Kalat. Mind and Brain, the Science of Psychology. California: Cengage Learning, 2014. Print.
3966:
654:
The AMY receives input from the VTA, and outputs to the NAc. The amygdala is important in creating powerful emotional
516:
3144:
Baliki, M. N.; Mansour, A.; Baria, A. T.; Huang, L.; Berger, S. E.; Fields, H. L.; Apkarian, A. V. (9 October 2013).
677:, whereas stimuli that are attractive and motivate approach behavior, but are not inherently pleasurable, are termed
1108:
translational paradigms, variable results may also lie in the heterogenous functionality of reward related regions.
6325:
5860:
1348:
3410:
Meyer, J. S., & Quenzer, L. F. (2013). Psychopharmacology: Drugs, the brain, and behavior. Sinauer Associates.
858:) requires the nucleus accumbens. Habitual and goal directed instrumental learning are dependent upon the lateral
6390:
6320:
6272:
6232:
6112:
5966:
2429:"Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in prefrontal cortex"
938:
335:
1236:
are inactivated. In this perspective, animals, like humans, engage in behaviors that increase dopamine release.
6582:
6073:
4710:"Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology"
1183:
1035:
482:
419:
375:
371:
1845:
1843:
1841:
1839:
1837:
1835:
1833:
5332:"Positive reinforcement produced by electrical stimulation of the septal area and other regions of rat brain"
140:
emotions. Thus, reward is a mechanism that evolved to help increase the adaptive fitness of animals. In drug
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6343:
5757:
1323:
1022:
775:
697:
478:
3146:"Parceling Human Accumbens into Putative Core and Shell Dissociates Encoding of Values for Reward and Pain"
573:
projecting to the prefrontal cortex, underpinning cognitive functions, such as learning external cues, etc.
569:
projecting to limbic (striatal) regions and underpinning the motivational behaviors and processes, and the
6395:
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6182:
6107:
6102:
5895:
1275:
1243:
1209:
1043:
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in the nucleus accumbens (NAcc), these structures are excited, "releasing" reward related behavior. While
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184:
168:
102:
98:
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1270:), and a placebo on reward responses to music – including the degree of pleasure experienced during
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parabrachial nucleus hotspot has only been demonstrated to respond to benzodiazepine receptor agonists.
407:
233:
226:
188:
4442:"Reconceptualizing anhedonia: novel perspectives on balancing the pleasure networks in the human brain"
66:
6557:
6380:
6237:
6048:
5925:
5902:
5844:
5781:
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5591:
4857:"The heterogeneity of ventral tegmental area neurons: Projection functions in a mood-related context"
4295:
3308:
3297:"Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation"
3098:
3016:
stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
2874:
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106:
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1282:) in human subjects. This research demonstrated that increased dopamine neurotransmission acts as a
802:, whereas the liking component is thought to be controlled by opiate-GABA-endocannabinoids systems.
6572:
6304:
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6137:
6132:
6122:
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3087:"In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward"
1343:
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949:
469:
363:
276:
160:
133:
4111:
3962:"Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator"
2079:
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is associated with deficits in motivation, commonly grouped under other negative symptoms such as
6542:
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6450:
6425:
6415:
6210:
6147:
6127:
5829:
5750:
5075:
5032:
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4168:
4041:
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Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?".
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and colleagues used nutrients inside the gut to stimulate the reward system via the vagus nerve.
1011:
999:
779:
771:
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655:
566:
435:
303:
192:
156:
86:
2372:"Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors"
4286:
Goeders N.E., Smith J.E. (1983). "Cortical dopaminergic involvement in cocaine reinforcement".
1065:
Dysfunctional motivational salience appears in a number of psychiatric symptoms and disorders.
980:, and reward cross-sensitization effects among specific addictive drugs and behaviors. Certain
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2409:
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2011:
1981:
1936:
1905:"The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans"
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such as dysregulation of reward processing and motivational dysfunction, including anhedonia.
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331:
299:
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125:
4616:
Zhang, B; Lin, P; Shi, H; Öngür, D; Auerbach, RP; Wang, X; Yao, S; Wang, X (September 2016).
3474:"Model-based and model-free Pavlovian reward learning: revaluation, revision, and revelation"
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less effort for rewards when compared with controls (Treadway et al. 2012; Yang et al. 2014)
4637:
4629:
4618:"Mapping anhedonia-specific dysfunction in a transdiagnostic approach: an ALE meta-analysis"
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1971:
1926:
1916:
1871:
1863:
1809:
1801:
1755:
1747:
1617:
1599:
1549:
1541:
1485:
1477:
1407:
1399:
1318:
1239:
1096:
1091:
904:
896:
721:
701:
458:
454:
447:
443:
379:
319:
295:
210:"liking" or pleasure component of reward include consummatory behavior and taking behavior.
4951:"Circuit-based frameworks of depressive behaviors: The role of reward circuitry and beyond"
543:
6469:
6353:
6078:
5824:
5819:
5309:
4591:
Preda, Adrian (2014). "Brain Imaging Correlates of Anhedonia". In Ritsner, Michael (ed.).
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4127:. Progress in Molecular Biology and Translational Science. Vol. 128. pp. 51–87.
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2936:"From prediction error to incentive salience: mesolimbic computation of reward motivation"
995:
524:
367:
327:
311:
307:
75:
Examples of primary rewards. Clockwise from top left: water, food, parental care, and sex.
46:
3914:
Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers
3711:"Contributions of ERK signaling in the striatum to instrumental learning and performance"
1224:
Animals quickly learn to press a bar to obtain an injection of opiates directly into the
17:
5661:
5595:
5284:
5085:
the latter one seems to be impaired . However, discrepant data have also been reported .
4299:
3960:
Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013).
3312:
3102:
2878:
2812:
2635:
1686:
1232:. The same animals do not work to obtain the opiates if the dopaminergic neurons of the
6526:
6335:
5867:
5804:
5680:
5645:
5614:
5579:
5552:
5527:
5486:
5461:
5401:
5248:
5213:
5188:
5161:
4975:
4950:
4926:
4905:
4881:
4872:
4856:
4832:
4807:
4783:
4758:
4734:
4709:
4642:
4617:
4568:
4543:
4519:
4492:
4468:
4441:
4382:
4373:
4357:
4222:
4203:
4151:
4132:
4085:
4060:
3988:
3961:
3890:
3865:
3779:
3762:
3735:
3710:
3686:
3661:
3637:
3612:
3581:
3498:
3473:
3449:
3424:
3378:
3353:
3329:
3296:
3272:
3247:
3170:
3145:
3121:
3086:
3057:
3032:
2960:
2935:
2831:
2796:
2599:
2575:"Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis"
2574:
2550:
2523:
2453:
2428:
2404:
2371:
2347:
2326:
2216:
2191:
2166:
2141:
2117:
2092:
2064:
2039:
1931:
1904:
1876:
1867:
1851:
1814:
1789:
1760:
1735:
1622:
1587:
1554:
1529:
1490:
1465:
1412:
1387:
1213:
965:
942:
733:
713:
339:
2886:
2675:
2658:
2489:
1169:
547:
Diagram showing some of the key components of the mesocorticolimbic ("reward") circuit
6536:
6348:
5773:
5737:
5003:"Progress in understanding mood disorders: optogenetic dissection of neural circuits"
4917:
4493:"Measuring anhedonia: impaired ability to pursue, experience, and learn about reward"
4418:
4029:
3881:
3440:
3232:
2951:
2590:
2338:
2038:
Richard JM, Castro DC, Difeliceantonio AG, Robinson MJ, Berridge KC (November 2013).
1712:
1271:
1123:
870:
866:
782:
is highly correlated with the magnitude of incentive salience for rewarding stimuli.
498:
323:
266:
262:
257:
The brain structures that compose the reward system are located primarily within the
5036:
4823:
4045:
3834:
3628:
3597:
3550:
3206:
2692:
2505:
2311:
2055:
1976:
1959:
778:(NAcc shell). The degree of dopamine neurotransmission into the NAcc shell from the
37:
5079:
5050:
Bucci, P; Galderisi, S (May 2017). "Categorizing and assessing negative symptoms".
4544:"Current perspectives on incentive salience and applications to clinical disorders"
3979:
3534:
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2444:
2387:
2268:
1604:
1284:
347:
280:
152:
4667:
Behavioral Neuroscience of Motivation (Current Topics in Behavioral Neurosciences)
5063:
4559:
3818:
3263:
2040:"Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley"
1805:
1545:
846:, while elicited actions that are insensitive to contingency or value are called
5809:
4808:"Reconsidering anhedonia in depression: lessons from translational neuroscience"
3369:
3354:"Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation"
1267:
1205:
1195:
1111:
1003:
528:
351:
343:
287:
269:
85:(the mesocorticolimbic circuit) is a group of neural structures responsible for
6521:
5650:
Proceedings of the National Academy of Sciences of the United States of America
5584:
Proceedings of the National Academy of Sciences of the United States of America
5477:
5310:"human nervous system | Description, Development, Anatomy, & Function"
3677:
3048:
2801:
Proceedings of the National Academy of Sciences of the United States of America
1481:
1403:
6420:
6260:
6097:
5543:
5460:
Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J; et al. (2018).
4966:
4633:
3726:
3489:
3248:"Dopamine's Effects on Corticostriatal Synapses during Reward-Based Behaviors"
2252:
2207:
2080:
Figure 3: Neural circuits underlying motivated 'wanting' and hedonic 'liking'.
1736:"Tribal love: the neural correlates of passionate engagement in football fans"
1338:
1190:
981:
838:
462:
399:
90:
5732:
5239:
5178:
4669:(1st ed.). Switzerland: Springer International Publishing. p. 343.
4509:
4458:
4123:
Hitchcock LN, Lattal KM (2014). "Histone-mediated epigenetics in addiction".
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1613:
1300:
This sensitization in the brain is similar to the effect of dopamine because
6163:
5789:
5777:
5670:
5604:
4708:
Salamone, JD; Yohn, SE; López-Cruz, L; San Miguel, N; Correa, M (May 2016).
4307:
3111:
2821:
1154:
1066:
1047:
1031:
989:
929:
466:
273:
148:
141:
5689:
5623:
5561:
5495:
5410:
5357:
5257:
5197:
5071:
5028:
4984:
4935:
4890:
4841:
4792:
4743:
4725:
4651:
4577:
4528:
4477:
4358:"Electrophysiological actions of nicotine on substantia nigra single units"
4231:
4160:
4094:
4037:
3997:
3942:
3899:
3826:
3788:
3744:
3695:
3646:
3589:
3542:
3507:
3458:
3387:
3338:
3281:
3224:
3179:
3130:
3066:
3000:(2nd ed.). New York: McGraw-Hill Medical. pp. 147–148, 367, 376.
2969:
2929:
2927:
2894:
2840:
2797:"Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula"
2684:
2608:
2559:
2497:
2462:
2413:
2356:
2303:
2260:
2225:
2175:
2126:
2073:
1985:
1940:
1885:
1823:
1769:
1631:
1563:
1499:
1421:
1157:
function are said to be key factors in ADHD. These impairments can lead to
232:
affect decision-making and induce approach behavior (via the assignment of
5292:
4426:
4391:
4342:
4315:
2643:
2142:"The cerebellum and addiction: insights gained from neuroimaging research"
2108:
1751:
793:
Robinson and Berridge's 1993 incentive-sensitization theory proposed that
5957:
5573:
5571:
5214:"Attention-deficit-hyperactivity disorder and reward deficiency syndrome"
2295:
1279:
1263:
1199:
1150:
934:
900:
859:
826:
745:
669:
577:
565:, either directly or indirectly. The VTA has two important pathways: The
473:
450:
423:
387:
359:
203:
121:
113:
3320:
2395:
57:
1921:
1333:
1194:
pleasurable sensations from such stimulation. When rats were tested in
985:
946:
762:
717:
501:
315:
199:
195:(i.e., motivation and "wanting", desire, or craving for a reward), and
109:
5230:
5019:
5002:
3215:
3033:"Neuroscience of affect: brain mechanisms of pleasure and displeasure"
2157:
2010:(2nd ed.). New York: McGraw-Hill Medical. pp. 365–366, 376.
147:
Primary rewards are a class of rewarding stimuli which facilitate the
6019:
5349:
3613:"Molecular substrates of action control in cortico-striatal circuits"
3246:
Bamford, Nigel S.; Wightman, R. Mark; Sulzer, David (February 2018).
2140:
Moulton EA, Elman I, Becerra LR, Goldstein RZ, Borsook D (May 2014).
725:
485:(i.e., reward derived from direct electrochemical stimulation of the
461:
to either stimulate (D1-like) or inhibit (D2-like) the production of
4774:
4076:
4198:. Handbook of Clinical Neurology. Vol. 148. pp. 747–765.
2998:
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
2996:
Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.).
2008:
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
2006:
Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.).
6029:
6024:
6014:
6009:
6004:
5998:
5991:
5984:
5952:
5937:
5528:"Affective neuroscience of pleasure: reward in humans and animals"
4542:
Olney, JJ; Warlow, SM; Naffziger, EE; Berridge, KC (August 2018).
1649:
1647:
1645:
1643:
1641:
1168:
912:
847:
761:
737:
4906:"Reward and aversion in a heterogeneous midbrain dopamine system"
2327:"Reward and aversion in a heterogeneous midbrain dopamine system"
681:. Extrinsic rewards (e.g., money) are rewarding as a result of a
402:
appear to modulate some forms of reward-related cognition (i.e.,
5947:
5942:
5931:
5271:
Wise RA (1996). "Addictive drugs and brain stimulation reward".
4194:
Walker DM, Nestler EJ (2018). "Neuroepigenetics and addiction".
4112:
Figure 4: Epigenetic basis of drug regulation of gene expression
3924:
3922:
2093:"Reward processing by the dorsal raphe nucleus: 5-HT and beyond"
1288:
condition for pleasurable hedonic reactions to music in humans.
1143:
908:
843:
27:
Group of neural structures responsible for motivation and desire
5746:
865:
During instrumental learning, opposing changes in the ratio of
493:
hypothalamus or ventral tegmental area, and that in inhibiting
286:, although other types of projection neurons contribute (e.g.,
5972:
3859:
3857:
1790:"The Mysterious Motivational Functions of Mesolimbic Dopamine"
1099:), while the more ventral sgACC is hyperactive in depression.
213:
The three primary functions of rewards are their capacity to:
117:
5580:"Dopamine modulates the reward experiences elicited by music"
1466:"Neuronal Reward and Decision Signals: From Theories to Data"
1388:"Neuronal reward and decision signals: from theories to data"
960:
common factor among virtually all forms of addiction (i.e.,
576:
Dopaminergic neurons in this region converts the amino acid
3866:"Natural rewards, neuroplasticity, and non-drug addictions"
2659:"Brain reward circuitry: insights from unsensed incentives"
2427:
Trantham-Davidson H, Neely LC, Lavin A, Seamans JK (2004).
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Yager LM, Garcia AF, Wunsch AM, Ferguson SM (August 2015).
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Kringelbach, Morten L.; Berridge, Kent C. (25 June 2010).
1852:"The ins and outs of the striatum: Role in drug addiction"
1685:
Brain & Behavior Research Foundation (13 March 2019).
5526:
Berridge, Kent C.; Kringelbach, Morten L. (August 2008).
2033:
2031:
1030:
targets in the nucleus accumbens and its local GABAergic
4061:"Transcriptional and epigenetic mechanisms of addiction"
2622:
Wise RA, Rompre PP (1989). "Brain dopamine and reward".
519:, which projects from the ventral tegmental area to the
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4440:
Rømer Thomsen, K; Whybrow, PC; Kringelbach, ML (2015).
4272:
Roy A. Wise, Drug-activation of brain reward pathways,
1208:
was a psychologist who used the reward system to study
584:, which is then converted to dopamine using the enzyme
5709:
Charney & Nestler's Neurobiology of Mental Illness
2370:
Nieh, EH; Kim, SY; Namburi, P; Tye, KM (20 May 2013).
911:, and increasing cellular excitability via inhibiting
481:, which is a set of many neural pathways that mediate
6498:
1189:
In a fundamental discovery made in 1954, researchers
89:(i.e., "wanting"; desire or craving for a reward and
6223:
Community reinforcement approach and family training
4356:
Clarke, Hommer D.W.; Pert A.; Skirboll L.R. (1985).
2001:
1999:
290:
projection neurons). The reward system includes the
6408:
6334:
6313:
6251:
6196:
6175:
6162:
6087:
6056:
6047:
5916:
5843:
5797:
5788:
5711:(5th ed.). New York: Oxford University Press.
5337:
Journal of Comparative and Physiological Psychology
5120:
5108:
5096:
4268:
4266:
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Epigenetics and Neuroplasticity—Evidence and Debate
3478:
Cognitive, Affective, & Behavioral Neuroscience
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3800:
3798:
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5135:"Never Enough? Why ADHD Brains Crave Stimulation"
4249:. Edinburgh: Churchill Livingstone. p. 596.
3756:
3754:
2790:
2788:
2786:
1523:
1521:
1519:
1517:
1515:
1513:
1511:
1509:
609:The Dorsal Striatum is involved in learning, the
4904:Lammel, S; Lim, BK; Malenka, RC (January 2014).
3611:Shiflett, MW; Balleine, BW (15 September 2011).
2325:Lammel, S; Lim, BK; Malenka, RC (January 2014).
1104:
835:operant conditioning (instrumental conditioning)
5160:Chandler DJ, Waterhouse BD, Gao WJ (May 2014).
5001:Lammel, S; Tye, KM; Warden, MR (January 2014).
3091:Proceedings of the National Academy of Sciences
1459:
1457:
1455:
831:classical conditioning (Pavlovian conditioning)
4996:
4994:
4759:"The brain reward circuitry in mood disorders"
2517:
2515:
1783:
1781:
1779:
1453:
1451:
1449:
1447:
1445:
1443:
1441:
1439:
1437:
1435:
968:) that induces addiction-related behavior and
5758:
5330:James Olds and Peter Milner (December 1954).
1598:(50). Society for Neuroscience: 12650–12660.
1095:be localized to more dorsal regions(i.e. the
489:), is also a component of the reward system.
8:
5508:: CS1 maint: multiple names: authors list (
4693:: CS1 maint: multiple names: authors list (
3709:Shiflett, MW; Balleine, BW (17 March 2011).
3418:
3416:
2795:Castro, DC; Berridge, KC (24 October 2017).
494:
5521:
5519:
5424:Ivan Petrovich Pavlov; G. V. Anrep (2003).
3031:Berridge KC, Kringelbach ML (1 June 2013).
2522:Castro, DC; Cole, SL; Berridge, KC (2015).
1740:Social Cognitive and Affective Neuroscience
899:, and through resulting phosphorylation of
259:cortico-basal ganglia-thalamo-cortical loop
6172:
6053:
5794:
5765:
5751:
5743:
5644:Goupil L, Aucouturier JJ (February 2019).
1660:(1st ed.). New York: Worth. pp.
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5669:
5613:
5603:
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5485:
5462:"A Neural Circuit for Gut-Induced Reward"
5400:
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4925:
4880:
4831:
4782:
4757:Russo, SJ; Nestler, EJ (September 2013).
4733:
4641:
4593:Anhedonia : a comprehensive handbook
4567:
4518:
4508:
4467:
4457:
4407:General Pharmacology: The Vascular System
4381:
4221:
4150:
4084:
3987:
3889:
3778:
3734:
3685:
3636:
3497:
3448:
3377:
3328:
3271:
3214:
3169:
3120:
3110:
3056:
2959:
2830:
2820:
2674:
2598:
2549:
2539:
2452:
2403:
2346:
2215:
2165:
2116:
2063:
1975:
1930:
1920:
1875:
1813:
1759:
1621:
1603:
1553:
1489:
1411:
1381:
1379:
1377:
1375:
1373:
1371:
1369:
1367:
1365:
4059:Robison AJ, Nestler EJ (November 2011).
3763:"Cellular basis of memory for addiction"
3195:Neuroscience & Biobehavioral Reviews
2747:
2745:
2743:
1528:Berridge KC, Kringelbach ML (May 2015).
1138:Attention deficit hyperactivity disorder
542:
6505:
5646:"Musical pleasure and musical emotions"
5325:
5323:
5304:
5302:
5133:Littman, Ph.D., Ellen (February 2017).
4949:Knowland, D; Lim, BK (5 January 2018).
4855:Walsh, JJ; Han, MH (12 December 2014).
4806:Treadway, MT; Zald, DH (January 2011).
2704:
2702:
1361:
862:and the medial striatum, respectively.
5501:
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5218:Neuropsychiatric Disease and Treatment
4955:Pharmacology Biochemistry and Behavior
4812:Neuroscience and Biobehavioral Reviews
4686:
4548:Current Opinion in Behavioral Sciences
4176:
4166:
2981:Cue as attractive motivational magnets
2241:Pharmacology Biochemistry and Behavior
1903:Taylor SB, Lewis CR, Olive MF (2013).
426:(both directly and indirectly via the
151:, and they include homeostatic (e.g.,
1657:An Introduction to Brain and Behavior
1654:Kolb, Bryan; Whishaw, Ian Q. (2001).
428:rostromedial tegmental nucleus (RMTg)
202:, particularly emotions that involve
7:
5430:. Courier Corporation. pp. 1–.
4446:Frontiers in Behavioral Neuroscience
3472:Dayan, P; Berridge, KC (June 2014).
3429:The European Journal of Neuroscience
2858:Kringelbach ML, Berridge KC (2012).
2573:Carlezon WA, Jr; Thomas, MJ (2009).
2091:Luo M, Zhou J, Liu Z (August 2015).
1958:Grall-Bronnec M, Sauvaget A (2014).
416:laterodorsal tegmental nucleus (LDT)
149:survival of one's self and offspring
6436:Discrimination against drug addicts
5285:10.1146/annurev.ne.19.030196.001535
4595:. Dordrecht: Springer Netherlands.
2977:Cue-triggered 'wanting' for the UCS
2636:10.1146/annurev.ps.40.020189.001203
633:environmental cues with the reward.
613:in goal directed learning, and the
6298:Tobacco cessation clinics in India
4873:10.1016/j.neuroscience.2014.06.006
4374:10.1111/j.1476-5381.1985.tb11081.x
4204:10.1016/B978-0-444-64076-5.00048-X
4133:10.1016/B978-0-12-800977-2.00003-6
3662:"Updating dopamine reward signals"
3582:10.1016/j.neuroscience.2014.04.026
1868:10.1016/j.neuroscience.2015.06.033
1254: ) tastes produced distinct
1092:subgenual cingulate cortex (sgACC)
25:
5121:Young, Anticevic & Barch 2018
5109:Young, Anticevic & Barch 2018
5097:Young, Anticevic & Barch 2018
2887:10.1038/scientificamerican0812-40
2528:Frontiers in Systems Neuroscience
1711:. 15 January 2008. Archived from
1705:"Dopamine Involved In Aggression"
6520:
6508:
6483:
6482:
6361:Low-threshold treatment programs
6228:Motivational enhancement therapy
4918:10.1016/j.neuropharm.2013.03.019
4030:10.1016/j.neuropharm.2015.09.023
3882:10.1016/j.neuropharm.2011.03.010
3441:10.1111/j.1460-9568.2008.06422.x
2952:10.1111/j.1460-9568.2012.07990.x
2591:10.1016/j.neuropharm.2008.06.075
2339:10.1016/j.neuropharm.2013.03.019
972:. In particular, ΔFosB promotes
243:emotions, particularly pleasure.
132:, rewarding stimuli function as
65:
56:
45:
36:
6441:Dopamine dysregulation syndrome
6431:Category:Vaccines against drugs
4824:10.1016/j.neubiorev.2010.06.006
3666:Current Opinion in Neurobiology
3629:10.1016/j.pneurobio.2011.05.007
3207:10.1016/j.neubiorev.2016.05.021
3037:Current Opinion in Neurobiology
2056:10.1016/j.neubiorev.2012.12.008
1977:10.1016/j.neubiorev.2014.10.013
1530:"Pleasure systems in the brain"
891:-type MSNs that constitute the
856:Pavlovian-instrumental transfer
430:) are also capable of inducing
420:pedunculopontine nucleus (PPTg)
3980:10.1523/JNEUROSCI.4881-12.2013
3535:10.1016/j.brainres.2014.12.023
3162:10.1523/JNEUROSCI.1731-13.2013
2445:10.1523/jneurosci.3179-04.2004
2388:10.1016/j.brainres.2012.11.001
1605:10.1523/jneurosci.1677-16.2016
1464:Schultz, Wolfram (July 2015).
1132:dorsolateral prefrontal cortex
1010:) due to their effects on the
112:, particularly ones involving
1:
6064:Adverse childhood experiences
5052:Current Opinion in Psychiatry
4714:Brain: A Journal of Neurology
2676:10.1016/S0896-6273(02)00965-0
2490:10.1016/s0306-4522(01)00379-7
1180:intracranial self-stimulation
873:receptors and phosphorylated
513:intracranial self-stimulation
414:) and behaviors as well. The
6293:Nicotine replacement therapy
6278:Intensive outpatient program
6266:Residential treatment center
6206:Cognitive behavioral therapy
5166:Frontiers in Neural Circuits
5064:10.1097/YCO.0000000000000322
4763:Nature Reviews. Neuroscience
4560:10.1016/j.cobeha.2018.01.007
4419:10.1016/0306-3623(83)90037-x
3819:10.3109/00952990.2014.933840
3761:Nestler EJ (December 2013).
3264:10.1016/j.neuron.2018.01.006
2284:Nature Reviews. Neuroscience
1806:10.1016/j.neuron.2012.10.021
1546:10.1016/j.neuron.2015.02.018
1274:, as measured by changes in
893:direct and indirect pathways
825:Rewarding stimuli can drive
593:Striatum (Nucleus Accumbens)
446:(i.e., neurons that use the
5891:Internet addiction disorder
5738:Scholarpedia Reward signals
4274:Drug and Alcohol Dependence
3967:The Journal of Neuroscience
3370:10.1523/ENEURO.0386-18.2018
2624:Annual Review of Psychology
2433:The Journal of Neuroscience
1592:The Journal of Neuroscience
688:The reward system contains
580:into DOPA using the enzyme
517:mesolimbic dopamine pathway
390:, and the remainder of the
116:as a core component (e.g.,
6599:
6326:List of twelve-step groups
5478:10.1016/j.cell.2018.08.049
4622:Brain Imaging and Behavior
3864:Olsen CM (December 2011).
3715:Behavioural Brain Research
3678:10.1016/j.conb.2012.11.012
3364:(2): ENEURO.0386–18.2018.
3049:10.1016/j.conb.2013.01.017
2934:Berridge KC (April 2012).
1687:"The Biology of Addiction"
1482:10.1152/physrev.00023.2014
1404:10.1152/physrev.00023.2014
1349:Wirehead (science fiction)
1295:hypothesis to address the
1178:This phenomenon is called
1128:reduced spontaneous speech
1097:pregenual cingulate cortex
1077:prefrontal cortex (mPFC).
1058:
927:
818:
755:
206:(i.e., hedonic "liking").
155:) and reproductive (e.g.,
6478:
6391:Supervised injection site
6321:Addiction recovery groups
6273:Heroin-assisted treatment
6233:Motivational interviewing
5544:10.1007/s00213-008-1099-6
5007:Genes, Brain and Behavior
4967:10.1016/j.pbb.2017.12.010
4634:10.1007/s11682-015-9457-6
3807:Am. J. Drug Alcohol Abuse
3727:10.1016/j.bbr.2010.12.010
3660:Schultz, W (April 2013).
3490:10.3758/s13415-014-0277-8
2253:10.1016/j.pbb.2017.05.001
2208:10.1007/s12311-016-0763-3
939:gene transcription factor
336:anterior cingulate cortex
18:Mesocorticolimbic circuit
6074:Psychological dependence
5908:Digital media addictions
5179:10.3389/fncir.2014.00053
4510:10.3389/fpsyg.2015.01409
4459:10.3389/fnbeh.2015.00049
3931:Ann. Agric. Environ. Med
3767:Dialogues Clin. Neurosci
3617:Progress in Neurobiology
2657:Wise RA (October 2002).
2541:10.3389/fnsys.2015.00090
1184:brain stimulation reward
1036:medial prefrontal cortex
483:brain stimulation reward
171:with intrinsic rewards.
6553:Behavioral neuroscience
6376:Needle exchange program
6366:Managed alcohol program
6344:Category:Harm reduction
5671:10.1073/pnas.1900369116
5605:10.1073/pnas.1811878116
5314:Encyclopedia Britannica
4497:Frontiers in Psychology
4331:J. Pharmacol. Exp. Ther
4308:10.1126/science.6879176
3150:Journal of Neuroscience
3112:10.1073/pnas.1521238113
2822:10.1073/pnas.1705753114
2044:Neurosci. Biobehav. Rev
1964:Neurosci. Biobehav. Rev
1324:Compliance (psychology)
1291:Berridge developed the
1280:hedonic impact of music
1023:medial forebrain bundle
1012:dopamine reward pathway
905:Ras-Raf-MEK-ERK pathway
776:nucleus accumbens shell
698:nucleus accumbens shell
615:Dorsal Lateral Striatum
479:medial forebrain bundle
169:classically conditioned
6548:Cognitive neuroscience
6396:Tobacco harm reduction
6216:Contingency management
6183:Alcohol detoxification
5896:Internet sex addiction
4196:Neurogenetics, Part II
1276:electrodermal activity
1244:affective neuroscience
1210:classical conditioning
1174:
1044:ventral tegmental area
768:
611:Dorsal Medial Striatum
559:ventral tegmental area
552:Ventral tegmental area
548:
424:lateral habenula (LHb)
292:ventral tegmental area
236:to rewarding stimuli);
223:classical conditioning
185:classical conditioning
103:classical conditioning
99:positive reinforcement
6563:Behavior modification
6458:Motivational salience
6386:Stimulant maintenance
6371:Moderation Management
6283:Methadone maintenance
3301:Nature Communications
2109:10.1101/lm.037317.114
2050:(9 Pt A): 1919–1931.
1470:Physiological Reviews
1392:Physiological Reviews
1256:orofacial expressions
1250: ) and bitter (
1172:
1159:executive dysfunction
1061:Motivational salience
962:behavioral addictions
819:Further information:
800:dopaminergic pathways
788:motivational salience
765:
546:
408:motivational salience
234:motivational salience
227:operant reinforcement
189:operant reinforcement
6381:Responsible drug use
6238:Motivational therapy
5903:Video game addiction
5427:Conditioned Reflexes
5141:. New Hope Media LLC
4726:10.1093/brain/aww050
4491:Thomsen, KR (2015).
2296:10.1038/nrn.2016.165
1715:on 23 September 2010
1246:, found that sweet (
1088:basolateral amygdala
1040:medium spiny neurons
1019:lateral hypothalamus
978:reward sensitization
950:medium spiny neurons
829:in both the form of
821:Associative learning
742:immediate early gene
710:orbitofrontal cortex
706:parabrachial nucleus
582:tyrosine hydroxylase
571:mesocortical pathway
506:basolateral amygdala
487:lateral hypothalamus
470:medium spiny neurons
404:associative learning
396:dorsal raphe nucleus
384:parabrachial nucleus
356:lateral hypothalamus
277:medium spiny neurons
219:associative learning
181:associative learning
134:positive reinforcers
130:operant conditioning
95:associative learning
6305:Twelve-step program
6188:Drug detoxification
6069:Physical dependence
5733:Scholarpedia Reward
5662:2019PNAS..116.3364G
5596:2019PNAS..116.3793F
5273:Annu. Rev. Neurosci
4300:1983Sci...221..773G
3321:10.1038/ncomms11829
3313:2016NatCo...711829S
3156:(41): 16383–16393.
3103:2016PNAS..113.2726C
2879:2012SciAm.307b..40K
2867:Scientific American
2813:2017PNAS..114E9125C
2807:(43): E9125–E9134.
2585:(Suppl 1): 122–32.
2439:(47): 10652–10659.
1909:Subst Abuse Rehabil
1752:10.1093/scan/nsx003
1344:Norm of reciprocity
974:self-administration
683:learned association
364:subthalamic nucleus
362:(multiple nuclei),
350:(particularly, the
241:positively-valenced
197:positively-valenced
165:learned association
161:parental investment
138:positively-valenced
107:positively-valenced
6463:Incentive salience
6451:Inhibitory control
6426:Category:Addiction
6416:Addiction medicine
6211:Relapse prevention
6148:Tanning dependence
5532:Psychopharmacology
5472:(3): 665–678.e23.
5389:Discovery Medicine
5364:on 5 February 2012
5316:. 23 January 2024.
5139:ADDditude Magazine
4912:. 76 Pt B: 351–9.
4065:Nat. Rev. Neurosci
2333:. 76 Pt B: 351–9.
1922:10.2147/SAR.S39684
1709:Medical News Today
1386:Schultz W (2015).
1329:Experience machine
1293:incentive salience
1242:, a researcher in
1234:mesolimbic pathway
1226:midbrain tegmentum
1175:
1002:are rewarding and
806:Anti-reward system
780:mesolimbic pathway
772:Incentive salience
769:
758:Incentive salience
752:Wanting and liking
734:induced expression
656:flashbulb memories
586:DOPA decarboxylase
567:mesolimbic pathway
549:
436:incentive salience
304:olfactory tubercle
284:projection neurons
193:incentive salience
87:incentive salience
6496:
6495:
6446:Cognitive control
6404:
6403:
6288:Smoking cessation
6243:Physical exercise
6158:
6157:
6144:Non-drug stimuli
6043:
6042:
5887:Internet-related
5437:978-0-486-43093-5
5231:10.2147/ndt.s2627
5020:10.1111/gbb.12049
4910:Neuropharmacology
4720:(Pt 5): 1325–47.
4676:978-3-319-26933-7
4602:978-94-017-8590-7
4294:(4612): 773–775.
4256:978-0-443-07145-4
4018:Neuropharmacology
3870:Neuropharmacology
3097:(10): 2726–2731.
3007:978-0-07-148127-4
2860:"The Joyful Mind"
2579:Neuropharmacology
2331:Neuropharmacology
2158:10.1111/adb.12101
2146:Addiction Biology
2017:978-0-07-148127-4
1230:nucleus accumbens
1071:aversive salience
984:modifications of
970:neural plasticity
954:nucleus accumbens
679:extrinsic rewards
675:intrinsic rewards
623:Prefrontal Cortex
563:nucleus accumbens
533:peripheral nerves
521:nucleus accumbens
459:D2-like receptors
455:D1-like receptors
444:dopamine pathways
432:aversive salience
412:positive emotions
392:extended amygdala
332:prefrontal cortex
300:nucleus accumbens
16:(Redirected from
6590:
6525:
6524:
6513:
6512:
6511:
6504:
6486:
6485:
6173:
6054:
5979:G9a-like protein
5795:
5767:
5760:
5753:
5744:
5722:
5698:
5697:
5683:
5673:
5656:(9): 3364–3366.
5641:
5632:
5631:
5617:
5607:
5590:(9): 3793–3798.
5575:
5566:
5565:
5555:
5523:
5514:
5513:
5507:
5499:
5489:
5457:
5451:
5448:
5442:
5441:
5421:
5415:
5414:
5404:
5380:
5374:
5373:
5371:
5369:
5360:. Archived from
5350:10.1037/h0058775
5327:
5318:
5317:
5306:
5297:
5296:
5268:
5262:
5261:
5251:
5233:
5208:
5202:
5201:
5191:
5181:
5157:
5151:
5150:
5148:
5146:
5130:
5124:
5118:
5112:
5106:
5100:
5094:
5088:
5087:
5047:
5041:
5040:
5022:
4998:
4989:
4988:
4978:
4946:
4940:
4939:
4929:
4901:
4895:
4894:
4884:
4852:
4846:
4845:
4835:
4803:
4797:
4796:
4786:
4754:
4748:
4747:
4737:
4705:
4699:
4698:
4692:
4684:
4662:
4656:
4655:
4645:
4613:
4607:
4606:
4588:
4582:
4581:
4571:
4539:
4533:
4532:
4522:
4512:
4488:
4482:
4481:
4471:
4461:
4437:
4431:
4430:
4402:
4396:
4395:
4385:
4362:Br. J. Pharmacol
4353:
4347:
4346:
4326:
4320:
4319:
4283:
4277:
4276:1998; 51 13–22.
4270:
4261:
4260:
4245:Rang HP (2003).
4242:
4236:
4235:
4225:
4191:
4185:
4184:
4178:
4174:
4172:
4164:
4154:
4120:
4114:
4109:
4107:gene repression.
4106:
4102:
4088:
4056:
4050:
4049:
4012:
4006:
4005:
3991:
3974:(8): 3434–3442.
3957:
3951:
3950:
3926:
3917:
3911:
3893:
3876:(7): 1109–1122.
3861:
3852:
3851:
3847:molecular switch
3802:
3793:
3792:
3782:
3758:
3749:
3748:
3738:
3706:
3700:
3699:
3689:
3657:
3651:
3650:
3640:
3608:
3602:
3601:
3565:
3559:
3558:
3529:(Pt A): 104–16.
3518:
3512:
3511:
3501:
3469:
3463:
3462:
3452:
3420:
3411:
3408:
3402:
3398:
3392:
3391:
3381:
3349:
3343:
3342:
3332:
3292:
3286:
3285:
3275:
3243:
3237:
3236:
3218:
3190:
3184:
3183:
3173:
3141:
3135:
3134:
3124:
3114:
3081:
3075:
3074:
3060:
3028:
3022:
3021:
2993:
2987:
2986:
2963:
2946:(7): 1124–1143.
2940:Eur. J. Neurosci
2931:
2922:
2921:
2911:
2909:
2904:on 29 March 2017
2903:
2897:. Archived from
2864:
2855:
2849:
2848:
2834:
2824:
2792:
2781:
2777:
2771:
2768:
2762:
2758:
2752:
2749:
2738:
2734:
2728:
2725:
2719:
2716:
2710:
2706:
2697:
2696:
2678:
2654:
2648:
2647:
2619:
2613:
2612:
2602:
2570:
2564:
2563:
2553:
2543:
2519:
2510:
2509:
2473:
2467:
2466:
2456:
2424:
2418:
2417:
2407:
2367:
2361:
2360:
2350:
2322:
2316:
2315:
2279:
2273:
2272:
2236:
2230:
2229:
2219:
2186:
2180:
2179:
2169:
2137:
2131:
2130:
2120:
2088:
2082:
2077:
2067:
2035:
2026:
2025:
2003:
1994:
1993:
1979:
1955:
1949:
1948:
1934:
1924:
1900:
1894:
1893:
1879:
1847:
1828:
1827:
1817:
1785:
1774:
1773:
1763:
1731:
1725:
1724:
1722:
1720:
1701:
1695:
1694:
1682:
1676:
1675:
1651:
1636:
1635:
1625:
1607:
1583:
1577:
1576:
1557:
1525:
1504:
1503:
1493:
1461:
1430:
1429:
1415:
1383:
1319:Carrot and stick
1106:
937:(DeltaFosB) – a
897:protein kinase A
722:endocannabinoids
702:ventral pallidum
694:hedonic hotspots
690:pleasure centers
663:Pleasure centers
604:Ventral Striatum
496:
448:neurotransmitter
380:ventral pallidum
320:substantia nigra
296:ventral striatum
69:
60:
49:
40:
21:
6598:
6597:
6593:
6592:
6591:
6589:
6588:
6587:
6583:Neuropsychology
6533:
6532:
6531:
6519:
6509:
6507:
6499:
6497:
6492:
6474:
6470:Sober companion
6400:
6354:Reagent testing
6330:
6309:
6253:
6247:
6198:
6192:
6167:
6165:
6154:
6083:
6039:
5926:Transcriptional
5918:
5912:
5839:
5825:Methylphenidate
5820:Methamphetamine
5784:
5771:
5729:
5719:
5705:
5702:
5701:
5643:
5642:
5635:
5577:
5576:
5569:
5525:
5524:
5517:
5500:
5459:
5458:
5454:
5449:
5445:
5438:
5423:
5422:
5418:
5395:(49): 579–587.
5382:
5381:
5377:
5367:
5365:
5329:
5328:
5321:
5308:
5307:
5300:
5270:
5269:
5265:
5210:
5209:
5205:
5159:
5158:
5154:
5144:
5142:
5132:
5131:
5127:
5119:
5115:
5107:
5103:
5095:
5091:
5049:
5048:
5044:
5000:
4999:
4992:
4948:
4947:
4943:
4903:
4902:
4898:
4854:
4853:
4849:
4805:
4804:
4800:
4775:10.1038/nrn3381
4756:
4755:
4751:
4707:
4706:
4702:
4685:
4677:
4664:
4663:
4659:
4615:
4614:
4610:
4603:
4590:
4589:
4585:
4541:
4540:
4536:
4490:
4489:
4485:
4439:
4438:
4434:
4404:
4403:
4399:
4355:
4354:
4350:
4328:
4327:
4323:
4285:
4284:
4280:
4271:
4264:
4257:
4244:
4243:
4239:
4214:
4193:
4192:
4188:
4175:
4165:
4143:
4122:
4121:
4117:
4110:
4104:
4100:
4077:10.1038/nrn3111
4071:(11): 623–637.
4058:
4057:
4053:
4014:
4013:
4009:
3959:
3958:
3954:
3928:
3927:
3920:
3912:
3863:
3862:
3855:
3844:
3842:
3839:
3804:
3803:
3796:
3760:
3759:
3752:
3708:
3707:
3703:
3659:
3658:
3654:
3610:
3609:
3605:
3567:
3566:
3562:
3520:
3519:
3515:
3471:
3470:
3466:
3422:
3421:
3414:
3409:
3405:
3399:
3395:
3351:
3350:
3346:
3294:
3293:
3289:
3245:
3244:
3240:
3192:
3191:
3187:
3143:
3142:
3138:
3083:
3082:
3078:
3030:
3029:
3025:
3017:
3014:
3008:
2995:
2994:
2990:
2982:
2980:
2978:
2976:
2933:
2932:
2925:
2918:
2916:
2907:
2905:
2901:
2862:
2857:
2856:
2852:
2794:
2793:
2784:
2778:
2774:
2769:
2765:
2759:
2755:
2750:
2741:
2735:
2731:
2726:
2722:
2717:
2713:
2707:
2700:
2656:
2655:
2651:
2621:
2620:
2616:
2572:
2571:
2567:
2521:
2520:
2513:
2475:
2474:
2470:
2426:
2425:
2421:
2369:
2368:
2364:
2324:
2323:
2319:
2281:
2280:
2276:
2238:
2237:
2233:
2188:
2187:
2183:
2139:
2138:
2134:
2090:
2089:
2085:
2078:
2037:
2036:
2029:
2018:
2005:
2004:
1997:
1957:
1956:
1952:
1902:
1901:
1897:
1849:
1848:
1831:
1787:
1786:
1777:
1733:
1732:
1728:
1718:
1716:
1703:
1702:
1698:
1684:
1683:
1679:
1672:
1653:
1652:
1639:
1585:
1584:
1580:
1527:
1526:
1507:
1463:
1462:
1433:
1385:
1384:
1363:
1358:
1353:
1314:
1266:), antagonist (
1222:
1167:
1149:Impairments of
1140:
1121:
1083:
1063:
1057:
996:Addictive drugs
966:drug addictions
932:
926:
921:
889:
882:
823:
817:
808:
760:
754:
665:
541:
525:natural rewards
368:globus pallidus
354:nucleus in the
328:pars reticulata
312:caudate nucleus
308:dorsal striatum
255:
250:
177:
79:
78:
77:
76:
72:
71:
70:
62:
61:
52:
51:
50:
42:
41:
28:
23:
22:
15:
12:
11:
5:
6596:
6594:
6586:
6585:
6580:
6575:
6570:
6565:
6560:
6555:
6550:
6545:
6535:
6534:
6530:
6529:
6517:
6494:
6493:
6491:
6490:
6479:
6476:
6475:
6473:
6472:
6467:
6466:
6465:
6455:
6454:
6453:
6443:
6438:
6433:
6428:
6423:
6418:
6412:
6410:
6406:
6405:
6402:
6401:
6399:
6398:
6393:
6388:
6383:
6378:
6373:
6368:
6363:
6358:
6357:
6356:
6346:
6340:
6338:
6336:Harm reduction
6332:
6331:
6329:
6328:
6323:
6317:
6315:
6314:Support groups
6311:
6310:
6308:
6307:
6302:
6301:
6300:
6295:
6285:
6280:
6275:
6270:
6269:
6268:
6257:
6255:
6249:
6248:
6246:
6245:
6240:
6235:
6230:
6225:
6220:
6219:
6218:
6213:
6202:
6200:
6194:
6193:
6191:
6190:
6185:
6179:
6177:
6176:Detoxification
6170:
6160:
6159:
6156:
6155:
6153:
6152:
6151:
6150:
6142:
6141:
6140:
6135:
6130:
6125:
6120:
6115:
6113:Benzodiazepine
6110:
6105:
6100:
6091:
6089:
6085:
6084:
6082:
6081:
6076:
6071:
6066:
6060:
6058:
6051:
6045:
6044:
6041:
6040:
6038:
6037:
6036:
6035:
6032:
6027:
6022:
6017:
6012:
6007:
6002:
5995:
5988:
5981:
5976:
5963:
5962:
5961:
5960:
5955:
5950:
5945:
5940:
5935:
5922:
5920:
5914:
5913:
5911:
5910:
5905:
5900:
5899:
5898:
5893:
5885:
5884:
5883:
5878:
5870:
5868:Palatable food
5865:
5864:
5863:
5858:
5849:
5847:
5841:
5840:
5838:
5837:
5832:
5827:
5822:
5817:
5812:
5807:
5801:
5799:
5792:
5786:
5785:
5772:
5770:
5769:
5762:
5755:
5747:
5741:
5740:
5735:
5728:
5727:External links
5725:
5724:
5723:
5717:
5700:
5699:
5633:
5567:
5538:(3): 457–480.
5515:
5452:
5443:
5436:
5416:
5375:
5344:(6): 419–427.
5319:
5298:
5263:
5224:(5): 893–918.
5203:
5152:
5125:
5113:
5101:
5089:
5058:(3): 201–208.
5042:
4990:
4941:
4896:
4847:
4798:
4749:
4700:
4675:
4657:
4608:
4601:
4583:
4534:
4483:
4432:
4413:(3): 321–325.
4397:
4368:(4): 827–835.
4348:
4337:(2): 592–600.
4321:
4278:
4262:
4255:
4237:
4212:
4186:
4177:|journal=
4141:
4115:
4051:
4007:
3952:
3937:(3): 491–496.
3918:
3853:
3813:(6): 428–437.
3794:
3773:(4): 431–443.
3750:
3701:
3652:
3603:
3560:
3523:Brain Research
3513:
3464:
3435:(8): 1437–48.
3412:
3403:
3393:
3344:
3287:
3258:(3): 494–510.
3238:
3185:
3136:
3076:
3043:(3): 294–303.
3023:
3006:
2988:
2923:
2850:
2782:
2772:
2763:
2753:
2739:
2729:
2720:
2711:
2698:
2669:(2): 229–240.
2649:
2614:
2565:
2511:
2484:(4): 629–639.
2468:
2419:
2376:Brain Research
2362:
2317:
2274:
2231:
2202:(1): 203–229.
2181:
2152:(3): 317–331.
2132:
2103:(9): 452–460.
2083:
2027:
2016:
1995:
1950:
1895:
1829:
1800:(3): 470–485.
1775:
1746:(5): 718–728.
1726:
1696:
1677:
1670:
1637:
1578:
1569:the number of
1540:(3): 646–664.
1505:
1476:(3): 853–951.
1431:
1398:(3): 853–951.
1360:
1359:
1357:
1354:
1352:
1351:
1346:
1341:
1336:
1331:
1326:
1321:
1315:
1313:
1310:
1272:musical chills
1221:
1218:
1214:Ivan De Araujo
1166:
1163:
1142:In those with
1139:
1136:
1120:
1117:
1082:
1081:Mood disorders
1079:
1059:Main article:
1056:
1053:
943:overexpression
928:Main article:
925:
922:
920:
917:
887:
880:
877:occurs in the
816:
813:
807:
804:
756:Main article:
753:
750:
714:insular cortex
664:
661:
660:
659:
646:
645:
635:
634:
630:
620:
619:
607:
600:
590:
589:
574:
540:
537:
340:insular cortex
254:
251:
249:
246:
245:
244:
237:
230:
176:
173:
157:sexual contact
153:palatable food
74:
73:
64:
63:
55:
54:
53:
44:
43:
35:
34:
33:
32:
31:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
6595:
6584:
6581:
6579:
6576:
6574:
6571:
6569:
6566:
6564:
6561:
6559:
6556:
6554:
6551:
6549:
6546:
6544:
6541:
6540:
6538:
6528:
6523:
6518:
6516:
6506:
6502:
6489:
6481:
6480:
6477:
6471:
6468:
6464:
6461:
6460:
6459:
6456:
6452:
6449:
6448:
6447:
6444:
6442:
6439:
6437:
6434:
6432:
6429:
6427:
6424:
6422:
6419:
6417:
6414:
6413:
6411:
6407:
6397:
6394:
6392:
6389:
6387:
6384:
6382:
6379:
6377:
6374:
6372:
6369:
6367:
6364:
6362:
6359:
6355:
6352:
6351:
6350:
6349:Drug checking
6347:
6345:
6342:
6341:
6339:
6337:
6333:
6327:
6324:
6322:
6319:
6318:
6316:
6312:
6306:
6303:
6299:
6296:
6294:
6291:
6290:
6289:
6286:
6284:
6281:
6279:
6276:
6274:
6271:
6267:
6264:
6263:
6262:
6259:
6258:
6256:
6250:
6244:
6241:
6239:
6236:
6234:
6231:
6229:
6226:
6224:
6221:
6217:
6214:
6212:
6209:
6208:
6207:
6204:
6203:
6201:
6195:
6189:
6186:
6184:
6181:
6180:
6178:
6174:
6171:
6169:
6161:
6149:
6146:
6145:
6143:
6139:
6136:
6134:
6131:
6129:
6126:
6124:
6121:
6119:
6116:
6114:
6111:
6109:
6106:
6104:
6101:
6099:
6096:
6095:
6093:
6092:
6090:
6086:
6080:
6077:
6075:
6072:
6070:
6067:
6065:
6062:
6061:
6059:
6055:
6052:
6050:
6046:
6033:
6031:
6028:
6026:
6023:
6021:
6018:
6016:
6013:
6011:
6008:
6006:
6003:
6001:
6000:
5996:
5994:
5993:
5989:
5987:
5986:
5982:
5980:
5977:
5975:
5974:
5970:
5969:
5968:
5965:
5964:
5959:
5956:
5954:
5951:
5949:
5946:
5944:
5941:
5939:
5936:
5934:
5933:
5929:
5928:
5927:
5924:
5923:
5921:
5915:
5909:
5906:
5904:
5901:
5897:
5894:
5892:
5889:
5888:
5886:
5882:
5879:
5877:
5874:
5873:
5871:
5869:
5866:
5862:
5859:
5857:
5854:
5853:
5851:
5850:
5848:
5846:
5842:
5836:
5833:
5831:
5828:
5826:
5823:
5821:
5818:
5816:
5813:
5811:
5808:
5806:
5803:
5802:
5800:
5796:
5793:
5791:
5787:
5783:
5779:
5775:
5774:Reinforcement
5768:
5763:
5761:
5756:
5754:
5749:
5748:
5745:
5739:
5736:
5734:
5731:
5730:
5726:
5720:
5718:9780190681425
5714:
5710:
5704:
5703:
5696:
5691:
5687:
5682:
5677:
5672:
5667:
5663:
5659:
5655:
5651:
5647:
5640:
5638:
5634:
5630:
5625:
5621:
5616:
5611:
5606:
5601:
5597:
5593:
5589:
5585:
5581:
5574:
5572:
5568:
5563:
5559:
5554:
5549:
5545:
5541:
5537:
5533:
5529:
5522:
5520:
5516:
5511:
5505:
5497:
5493:
5488:
5483:
5479:
5475:
5471:
5467:
5463:
5456:
5453:
5447:
5444:
5439:
5433:
5429:
5428:
5420:
5417:
5412:
5408:
5403:
5398:
5394:
5390:
5386:
5379:
5376:
5363:
5359:
5355:
5351:
5347:
5343:
5339:
5338:
5333:
5326:
5324:
5320:
5315:
5311:
5305:
5303:
5299:
5294:
5290:
5286:
5282:
5278:
5274:
5267:
5264:
5259:
5255:
5250:
5245:
5241:
5237:
5232:
5227:
5223:
5219:
5215:
5207:
5204:
5199:
5195:
5190:
5185:
5180:
5175:
5171:
5167:
5163:
5156:
5153:
5140:
5136:
5129:
5126:
5122:
5117:
5114:
5110:
5105:
5102:
5098:
5093:
5090:
5086:
5081:
5077:
5073:
5069:
5065:
5061:
5057:
5053:
5046:
5043:
5038:
5034:
5030:
5026:
5021:
5016:
5012:
5008:
5004:
4997:
4995:
4991:
4986:
4982:
4977:
4972:
4968:
4964:
4960:
4956:
4952:
4945:
4942:
4937:
4933:
4928:
4923:
4919:
4915:
4911:
4907:
4900:
4897:
4892:
4888:
4883:
4878:
4874:
4870:
4866:
4862:
4858:
4851:
4848:
4843:
4839:
4834:
4829:
4825:
4821:
4818:(3): 537–55.
4817:
4813:
4809:
4802:
4799:
4794:
4790:
4785:
4780:
4776:
4772:
4769:(9): 609–25.
4768:
4764:
4760:
4753:
4750:
4745:
4741:
4736:
4731:
4727:
4723:
4719:
4715:
4711:
4704:
4701:
4696:
4690:
4683:
4678:
4672:
4668:
4661:
4658:
4653:
4649:
4644:
4639:
4635:
4631:
4628:(3): 920–39.
4627:
4623:
4619:
4612:
4609:
4604:
4598:
4594:
4587:
4584:
4579:
4575:
4570:
4565:
4561:
4557:
4553:
4549:
4545:
4538:
4535:
4530:
4526:
4521:
4516:
4511:
4506:
4502:
4498:
4494:
4487:
4484:
4479:
4475:
4470:
4465:
4460:
4455:
4451:
4447:
4443:
4436:
4433:
4428:
4424:
4420:
4416:
4412:
4408:
4401:
4398:
4393:
4389:
4384:
4379:
4375:
4371:
4367:
4363:
4359:
4352:
4349:
4344:
4340:
4336:
4332:
4325:
4322:
4317:
4313:
4309:
4305:
4301:
4297:
4293:
4289:
4282:
4279:
4275:
4269:
4267:
4263:
4258:
4252:
4248:
4241:
4238:
4233:
4229:
4224:
4219:
4215:
4213:9780444640765
4209:
4205:
4201:
4197:
4190:
4187:
4182:
4170:
4162:
4158:
4153:
4148:
4144:
4142:9780128009772
4138:
4134:
4130:
4126:
4119:
4116:
4113:
4108:
4096:
4092:
4087:
4082:
4078:
4074:
4070:
4066:
4062:
4055:
4052:
4047:
4043:
4039:
4035:
4031:
4027:
4023:
4019:
4011:
4008:
4004:
3999:
3995:
3990:
3985:
3981:
3977:
3973:
3969:
3968:
3963:
3956:
3953:
3949:
3944:
3940:
3936:
3932:
3925:
3923:
3919:
3915:
3910:
3907:
3901:
3897:
3892:
3887:
3883:
3879:
3875:
3871:
3867:
3860:
3858:
3854:
3850:
3848:
3836:
3832:
3828:
3824:
3820:
3816:
3812:
3808:
3801:
3799:
3795:
3790:
3786:
3781:
3776:
3772:
3768:
3764:
3757:
3755:
3751:
3746:
3742:
3737:
3732:
3728:
3724:
3720:
3716:
3712:
3705:
3702:
3697:
3693:
3688:
3683:
3679:
3675:
3672:(2): 229–38.
3671:
3667:
3663:
3656:
3653:
3648:
3644:
3639:
3634:
3630:
3626:
3622:
3618:
3614:
3607:
3604:
3599:
3595:
3591:
3587:
3583:
3579:
3575:
3571:
3564:
3561:
3557:
3552:
3548:
3544:
3540:
3536:
3532:
3528:
3524:
3517:
3514:
3509:
3505:
3500:
3495:
3491:
3487:
3484:(2): 473–92.
3483:
3479:
3475:
3468:
3465:
3460:
3456:
3451:
3446:
3442:
3438:
3434:
3430:
3426:
3419:
3417:
3413:
3407:
3404:
3397:
3394:
3389:
3385:
3380:
3375:
3371:
3367:
3363:
3359:
3355:
3348:
3345:
3340:
3336:
3331:
3326:
3322:
3318:
3314:
3310:
3306:
3302:
3298:
3291:
3288:
3283:
3279:
3274:
3269:
3265:
3261:
3257:
3253:
3249:
3242:
3239:
3234:
3230:
3226:
3222:
3217:
3212:
3208:
3204:
3200:
3196:
3189:
3186:
3181:
3177:
3172:
3167:
3163:
3159:
3155:
3151:
3147:
3140:
3137:
3132:
3128:
3123:
3118:
3113:
3108:
3104:
3100:
3096:
3092:
3088:
3080:
3077:
3073:
3068:
3064:
3059:
3054:
3050:
3046:
3042:
3038:
3034:
3027:
3024:
3020:
3009:
3003:
2999:
2992:
2989:
2985:
2971:
2967:
2962:
2957:
2953:
2949:
2945:
2941:
2937:
2930:
2928:
2924:
2920:
2900:
2896:
2892:
2888:
2884:
2880:
2876:
2872:
2868:
2861:
2854:
2851:
2847:
2842:
2838:
2833:
2828:
2823:
2818:
2814:
2810:
2806:
2802:
2798:
2791:
2789:
2787:
2783:
2776:
2773:
2767:
2764:
2757:
2754:
2748:
2746:
2744:
2740:
2733:
2730:
2724:
2721:
2715:
2712:
2705:
2703:
2699:
2694:
2690:
2686:
2682:
2677:
2672:
2668:
2664:
2660:
2653:
2650:
2645:
2641:
2637:
2633:
2629:
2625:
2618:
2615:
2610:
2606:
2601:
2596:
2592:
2588:
2584:
2580:
2576:
2569:
2566:
2561:
2557:
2552:
2547:
2542:
2537:
2533:
2529:
2525:
2518:
2516:
2512:
2507:
2503:
2499:
2495:
2491:
2487:
2483:
2479:
2472:
2469:
2464:
2460:
2455:
2450:
2446:
2442:
2438:
2434:
2430:
2423:
2420:
2415:
2411:
2406:
2401:
2397:
2393:
2389:
2385:
2381:
2377:
2373:
2366:
2363:
2358:
2354:
2349:
2344:
2340:
2336:
2332:
2328:
2321:
2318:
2313:
2309:
2305:
2301:
2297:
2293:
2289:
2285:
2278:
2275:
2270:
2266:
2262:
2258:
2254:
2250:
2246:
2242:
2235:
2232:
2227:
2223:
2218:
2213:
2209:
2205:
2201:
2197:
2193:
2185:
2182:
2177:
2173:
2168:
2163:
2159:
2155:
2151:
2147:
2143:
2136:
2133:
2128:
2124:
2119:
2114:
2110:
2106:
2102:
2098:
2094:
2087:
2084:
2081:
2075:
2071:
2066:
2061:
2057:
2053:
2049:
2045:
2041:
2034:
2032:
2028:
2024:
2019:
2013:
2009:
2002:
2000:
1996:
1992:
1987:
1983:
1978:
1973:
1969:
1965:
1961:
1954:
1951:
1947:
1942:
1938:
1933:
1928:
1923:
1918:
1914:
1910:
1906:
1899:
1896:
1892:
1887:
1883:
1878:
1873:
1869:
1865:
1861:
1857:
1853:
1846:
1844:
1842:
1840:
1838:
1836:
1834:
1830:
1825:
1821:
1816:
1811:
1807:
1803:
1799:
1795:
1791:
1784:
1782:
1780:
1776:
1771:
1767:
1762:
1757:
1753:
1749:
1745:
1741:
1737:
1730:
1727:
1714:
1710:
1706:
1700:
1697:
1692:
1688:
1681:
1678:
1673:
1671:9780716751694
1667:
1663:
1659:
1658:
1650:
1648:
1646:
1644:
1642:
1638:
1633:
1629:
1624:
1619:
1615:
1611:
1606:
1601:
1597:
1593:
1589:
1582:
1579:
1575:
1572:
1565:
1561:
1556:
1551:
1547:
1543:
1539:
1535:
1531:
1524:
1522:
1520:
1518:
1516:
1514:
1512:
1510:
1506:
1501:
1497:
1492:
1487:
1483:
1479:
1475:
1471:
1467:
1460:
1458:
1456:
1454:
1452:
1450:
1448:
1446:
1444:
1442:
1440:
1438:
1436:
1432:
1428:
1423:
1419:
1414:
1409:
1405:
1401:
1397:
1393:
1389:
1382:
1380:
1378:
1376:
1374:
1372:
1370:
1368:
1366:
1362:
1355:
1350:
1347:
1345:
1342:
1340:
1337:
1335:
1332:
1330:
1327:
1325:
1322:
1320:
1317:
1316:
1311:
1309:
1307:
1303:
1298:
1294:
1289:
1287:
1286:
1281:
1277:
1273:
1269:
1265:
1261:
1257:
1253:
1249:
1245:
1241:
1240:Kent Berridge
1237:
1235:
1231:
1227:
1220:Other species
1219:
1217:
1215:
1211:
1207:
1203:
1201:
1197:
1196:Skinner boxes
1192:
1187:
1185:
1181:
1171:
1164:
1162:
1160:
1156:
1152:
1147:
1145:
1137:
1135:
1133:
1129:
1125:
1124:Schizophrenia
1119:Schizophrenia
1118:
1116:
1113:
1109:
1100:
1098:
1093:
1089:
1080:
1078:
1074:
1072:
1068:
1062:
1054:
1052:
1049:
1045:
1041:
1037:
1033:
1029:
1024:
1020:
1015:
1013:
1009:
1005:
1001:
997:
993:
991:
987:
983:
979:
975:
971:
967:
963:
959:
955:
951:
948:
944:
940:
936:
931:
923:
918:
916:
914:
910:
906:
902:
898:
894:
890:
883:
876:
872:
868:
863:
861:
857:
851:
849:
845:
844:goal-directed
840:
836:
832:
828:
822:
814:
812:
805:
803:
801:
796:
791:
789:
783:
781:
777:
773:
764:
759:
751:
749:
747:
743:
739:
735:
730:
727:
723:
719:
715:
711:
707:
703:
699:
695:
691:
686:
684:
680:
676:
671:
667:
662:
657:
653:
652:
651:
650:
642:
641:
640:
639:
631:
627:
626:
625:
624:
616:
612:
608:
605:
601:
597:
596:
595:
594:
587:
583:
579:
575:
572:
568:
564:
560:
556:
555:
554:
553:
545:
538:
536:
534:
530:
526:
522:
518:
514:
509:
507:
503:
500:
499:GABA receptor
490:
488:
484:
480:
475:
471:
468:
464:
460:
456:
452:
449:
445:
440:
437:
433:
429:
425:
421:
417:
413:
409:
405:
401:
397:
393:
389:
385:
381:
377:
373:
369:
365:
361:
357:
353:
349:
345:
341:
337:
333:
329:
325:
324:pars compacta
321:
317:
313:
309:
305:
301:
297:
293:
289:
285:
282:
278:
275:
271:
268:
267:glutamatergic
264:
263:basal ganglia
260:
252:
247:
242:
238:
235:
231:
228:
224:
220:
216:
215:
214:
211:
207:
205:
201:
198:
194:
190:
186:
182:
174:
172:
170:
166:
162:
158:
154:
150:
145:
143:
139:
135:
131:
127:
123:
119:
115:
111:
108:
104:
100:
96:
92:
88:
84:
83:reward system
68:
59:
48:
39:
30:
19:
6578:Neuroanatomy
5997:
5990:
5983:
5971:
5930:
5872:Sex-related
5708:
5693:
5653:
5649:
5627:
5587:
5583:
5535:
5531:
5504:cite journal
5469:
5465:
5455:
5446:
5426:
5419:
5392:
5388:
5378:
5366:. Retrieved
5362:the original
5341:
5335:
5313:
5276:
5272:
5266:
5221:
5217:
5206:
5169:
5165:
5155:
5143:. Retrieved
5138:
5128:
5116:
5104:
5092:
5083:
5055:
5051:
5045:
5013:(1): 38–51.
5010:
5006:
4958:
4954:
4944:
4909:
4899:
4864:
4861:Neuroscience
4860:
4850:
4815:
4811:
4801:
4766:
4762:
4752:
4717:
4713:
4703:
4680:
4666:
4660:
4625:
4621:
4611:
4592:
4586:
4551:
4547:
4537:
4500:
4496:
4486:
4449:
4445:
4435:
4410:
4406:
4400:
4365:
4361:
4351:
4334:
4330:
4324:
4291:
4287:
4281:
4273:
4247:Pharmacology
4246:
4240:
4195:
4189:
4124:
4118:
4098:
4068:
4064:
4054:
4021:
4017:
4010:
4001:
3971:
3965:
3955:
3946:
3934:
3930:
3903:
3873:
3869:
3846:
3838:
3810:
3806:
3770:
3766:
3721:(1): 240–7.
3718:
3714:
3704:
3669:
3665:
3655:
3620:
3616:
3606:
3573:
3570:Neuroscience
3569:
3563:
3554:
3526:
3522:
3516:
3481:
3477:
3467:
3432:
3428:
3406:
3396:
3361:
3357:
3347:
3307:(1): 11829.
3304:
3300:
3290:
3255:
3251:
3241:
3198:
3194:
3188:
3153:
3149:
3139:
3094:
3090:
3079:
3070:
3040:
3036:
3026:
3011:
2997:
2991:
2973:
2943:
2939:
2913:
2906:. Retrieved
2899:the original
2873:(2): 44–45.
2870:
2866:
2853:
2844:
2804:
2800:
2775:
2766:
2756:
2732:
2723:
2714:
2666:
2662:
2652:
2627:
2623:
2617:
2582:
2578:
2568:
2531:
2527:
2481:
2478:Neuroscience
2477:
2471:
2436:
2432:
2422:
2396:1721.1/92890
2379:
2375:
2365:
2330:
2320:
2290:(2): 73–85.
2287:
2283:
2277:
2244:
2240:
2234:
2199:
2195:
2184:
2149:
2145:
2135:
2100:
2096:
2086:
2047:
2043:
2021:
2007:
1989:
1967:
1963:
1953:
1944:
1912:
1908:
1898:
1889:
1859:
1856:Neuroscience
1855:
1797:
1793:
1743:
1739:
1729:
1717:. Retrieved
1713:the original
1708:
1699:
1690:
1680:
1656:
1595:
1591:
1581:
1570:
1567:
1537:
1533:
1473:
1469:
1425:
1395:
1391:
1305:
1301:
1296:
1290:
1285:sine qua non
1283:
1259:
1251:
1247:
1238:
1223:
1204:
1188:
1176:
1155:serotonergic
1151:dopaminergic
1148:
1141:
1122:
1110:
1101:
1084:
1075:
1064:
1016:
1007:
994:
957:
933:
864:
852:
824:
809:
794:
792:
784:
770:
731:
693:
689:
687:
678:
674:
668:
666:
648:
647:
637:
636:
622:
621:
614:
610:
603:
592:
591:
570:
551:
550:
510:
491:
442:Most of the
441:
348:hypothalamus
281:dopaminergic
279:(MSNs), and
270:interneurons
256:
248:Neuroanatomy
212:
208:
178:
146:
82:
80:
29:
6558:Behaviorism
6197:Behavioral
6108:Barbiturate
6103:Amphetamine
5881:Pornography
5876:Intercourse
5810:Amphetamine
5776:disorders:
5279:: 319–340.
4024:: 154–164.
3843:Conclusions
3623:(1): 1–13.
3201:: 370–386.
2630:: 191–225.
1970:: 592–613.
1862:: 529–541.
1719:14 November
1268:risperidone
1206:Ivan Pavlov
1173:Skinner box
1112:Optogenetic
1006:(i.e., are
1004:reinforcing
712:(OFC), and
638:Hippocampus
539:Key pathway
529:drug reward
352:orexinergic
344:hippocampus
322:(i.e., the
310:(i.e., the
298:(i.e., the
288:orexinergic
183:(primarily
97:(primarily
6573:Motivation
6537:Categories
6515:Psychology
6421:Allen Carr
6261:Drug rehab
6252:Treatment
6168:management
6164:Treatment
6098:Alcoholism
6079:Withdrawal
6049:Dependence
5967:Epigenetic
5919:mechanisms
5852:Financial
5845:Behavioral
5782:dependence
3216:1822/47044
2908:17 January
2196:Cerebellum
2097:Learn. Mem
1356:References
1339:Motivation
1191:James Olds
1055:Motivation
990:addictions
982:epigenetic
884:-type and
839:reinforcer
400:cerebellum
175:Definition
91:motivation
6543:Addiction
6199:therapies
6088:Disorders
5790:Addiction
5778:addiction
5240:1176-6328
4961:: 42–52.
4867:: 101–8.
4689:cite book
4554:: 59–69.
4179:ignored (
4169:cite book
3906:Komisaruk
3576:: 49–59.
3233:207092810
2382:: 73–92.
1915:: 29–43.
1614:0270-6474
1134:(DLPFC).
1067:Anhedonia
1048:afferents
1032:afferents
1008:addictive
1000:behaviors
930:Addiction
924:Addiction
919:Disorders
692: or
644:triggers.
599:striatum.
467:GABAergic
274:GABAergic
142:addiction
6568:Dopamine
6488:Category
6409:See also
6254:programs
6133:Nicotine
6123:Cannabis
6118:Caffeine
6057:Concepts
5917:Cellular
5861:Shopping
5856:Gambling
5830:Nicotine
5690:30770455
5624:30670642
5562:18311558
5496:30245012
5411:20587348
5368:26 April
5358:13233369
5258:19183781
5198:24904299
5072:28212174
5037:18542868
5029:23682971
4985:29309799
4936:23578393
4891:24931766
4842:20603146
4793:23942470
4744:27189581
4652:26487590
4578:29503841
4529:26441781
4503:: 1409.
4478:25814941
4232:29478612
4161:25410541
4095:21989194
4046:25317397
4038:26391065
3998:23426671
3943:23020045
3900:21459101
3835:19157711
3827:25083822
3789:24459410
3745:21147168
3696:23267662
3647:21704115
3598:21652525
3590:24769227
3551:11776683
3543:25514336
3508:24647659
3459:18793321
3388:29780881
3339:27337658
3282:29420932
3225:27235078
3180:24107968
3131:26831103
3067:23375169
2970:22487042
2895:22844850
2841:29073109
2780:467–476.
2761:515-533.
2737:505-512.
2693:16547037
2685:12383779
2609:18675281
2560:26124708
2506:33615497
2498:11720786
2463:15564581
2414:23142759
2357:23578393
2312:10311562
2304:28053327
2261:28476484
2247:: 9–22.
2226:26873754
2176:24851284
2127:26286655
2074:23261404
1986:25454360
1941:24648786
1886:26116518
1824:23141060
1770:28338882
1632:27974615
1564:25950633
1500:26109341
1422:26109341
1312:See also
1264:levodopa
1252:disliked
1200:dopamine
1028:efferent
901:DARPP-32
860:striatum
827:learning
815:Learning
746:euphoria
670:Pleasure
649:Amygdala
629:stimuli.
578:tyrosine
502:agonists
474:striatum
451:dopamine
388:amygdala
376:internal
372:external
360:thalamus
253:Overview
217:produce
204:pleasure
200:emotions
122:euphoria
114:pleasure
110:emotions
6527:Biology
6501:Portals
6128:Cocaine
5815:Cocaine
5805:Alcohol
5681:6397567
5658:Bibcode
5615:6397525
5592:Bibcode
5553:3004012
5487:6195474
5402:3008353
5293:8833446
5249:2626918
5189:4033238
5080:9923114
4976:6340396
4927:3778102
4882:4339667
4833:3005986
4784:3867253
4735:5839596
4643:4838562
4569:5831552
4520:4585007
4469:4356228
4427:6135645
4392:4041681
4383:1916681
4343:8496810
4316:6879176
4296:Bibcode
4288:Science
4223:5868351
4152:5914502
4086:3272277
3989:3865508
3891:3139704
3780:3898681
3736:3022085
3687:3866681
3638:3175490
3499:4074442
3450:2756656
3401:467–476
3379:5957524
3330:4931006
3309:Bibcode
3273:5808590
3171:3792469
3122:4791010
3099:Bibcode
3058:3644539
2961:3325516
2875:Bibcode
2846:impact.
2832:5664503
2809:Bibcode
2644:2648975
2600:2635333
2551:4466441
2454:5509068
2405:4099056
2348:3778102
2269:5089422
2217:5243918
2167:4031616
2118:4561406
2065:3706488
1932:3931688
1877:4523218
1815:4450094
1761:5460049
1691:YouTube
1662:438–441
1623:6705659
1555:4425246
1491:4491543
1413:4491543
1334:Frisson
1302:wanting
1297:wanting
1228:or the
1165:History
986:histone
958:crucial
956:is the
952:of the
947:D1-type
945:in the
718:opioids
472:of the
316:putamen
239:elicit
221:(i.e.,
126:ecstasy
105:), and
6138:Opioid
6094:Drugs
6020:HDAC10
5835:Opioid
5715:
5688:
5678:
5622:
5612:
5560:
5550:
5494:
5484:
5434:
5409:
5399:
5356:
5291:
5256:
5246:
5238:
5196:
5186:
5172:: 53.
5145:27 May
5078:
5070:
5035:
5027:
4983:
4973:
4934:
4924:
4889:
4879:
4840:
4830:
4791:
4781:
4742:
4732:
4673:
4650:
4640:
4599:
4576:
4566:
4527:
4517:
4476:
4466:
4452:: 49.
4425:
4390:
4380:
4341:
4314:
4253:
4230:
4220:
4210:
4159:
4149:
4139:
4093:
4083:
4044:
4036:
3996:
3986:
3941:
3898:
3888:
3833:
3825:
3787:
3777:
3743:
3733:
3694:
3684:
3645:
3635:
3596:
3588:
3549:
3541:
3506:
3496:
3457:
3447:
3386:
3376:
3358:eNeuro
3337:
3327:
3280:
3270:
3252:Neuron
3231:
3223:
3178:
3168:
3129:
3119:
3065:
3055:
3004:
2968:
2958:
2893:
2839:
2829:
2691:
2683:
2663:Neuron
2642:
2607:
2597:
2558:
2548:
2534:: 90.
2504:
2496:
2461:
2451:
2412:
2402:
2355:
2345:
2310:
2302:
2267:
2259:
2224:
2214:
2174:
2164:
2125:
2115:
2072:
2062:
2014:
1984:
1939:
1929:
1884:
1874:
1822:
1812:
1794:Neuron
1768:
1758:
1668:
1630:
1620:
1612:
1571:liking
1562:
1552:
1534:Neuron
1498:
1488:
1420:
1410:
1306:liking
1260:liking
848:habits
795:reward
726:orexin
724:, and
527:, and
465:. The
422:, and
410:, and
394:. The
370:(both
261:; the
6030:SIRT2
6025:SIRT1
6015:HDAC9
6010:HDAC5
6005:HDAC4
5999:HDAC3
5992:HDAC2
5985:HDAC1
5958:NF-κB
5953:GluR2
5938:c-Fos
5932:ΔFosB
5076:S2CID
5033:S2CID
4105:c-fos
4101:c-fos
4042:S2CID
3831:S2CID
3594:S2CID
3547:S2CID
3229:S2CID
2902:(PDF)
2863:(PDF)
2689:S2CID
2502:S2CID
2308:S2CID
2265:S2CID
1248:liked
935:ΔFosB
913:Kv4.2
740:, an
738:c-Fos
6166:and
5948:CREB
5943:Cdk5
5798:Drug
5780:and
5713:ISBN
5686:PMID
5620:PMID
5558:PMID
5510:link
5492:PMID
5466:Cell
5432:ISBN
5407:PMID
5370:2011
5354:PMID
5289:PMID
5254:PMID
5236:ISSN
5194:PMID
5147:2021
5068:PMID
5025:PMID
4981:PMID
4932:PMID
4887:PMID
4838:PMID
4789:PMID
4740:PMID
4695:link
4671:ISBN
4648:PMID
4597:ISBN
4574:PMID
4525:PMID
4474:PMID
4423:PMID
4388:PMID
4339:PMID
4312:PMID
4251:ISBN
4228:PMID
4208:ISBN
4181:help
4157:PMID
4137:ISBN
4091:PMID
4034:PMID
3994:PMID
3939:PMID
3896:PMID
3823:PMID
3785:PMID
3741:PMID
3692:PMID
3643:PMID
3586:PMID
3539:PMID
3527:1628
3504:PMID
3455:PMID
3384:PMID
3335:PMID
3278:PMID
3221:PMID
3176:PMID
3127:PMID
3063:PMID
3002:ISBN
2966:PMID
2910:2017
2891:PMID
2837:PMID
2681:PMID
2640:PMID
2605:PMID
2556:PMID
2494:PMID
2459:PMID
2410:PMID
2380:1511
2353:PMID
2300:PMID
2257:PMID
2222:PMID
2172:PMID
2123:PMID
2070:PMID
2012:ISBN
1982:PMID
1937:PMID
1882:PMID
1820:PMID
1766:PMID
1721:2010
1666:ISBN
1628:PMID
1610:ISSN
1560:PMID
1496:PMID
1418:PMID
1304:and
1153:and
1144:ADHD
1105:mPFC
1090:and
1026:its
1021:and
1017:The
998:and
964:and
909:CREB
871:NMDA
867:AMPA
833:and
602:The
557:The
495:MSNs
463:cAMP
434:and
398:and
374:and
326:and
314:and
302:and
225:and
187:and
159:and
124:and
101:and
81:The
6034:...
5973:G9a
5676:PMC
5666:doi
5654:116
5610:PMC
5600:doi
5588:116
5548:PMC
5540:doi
5536:199
5482:PMC
5474:doi
5470:175
5397:PMC
5346:doi
5281:doi
5244:PMC
5226:doi
5184:PMC
5174:doi
5060:doi
5015:doi
4971:PMC
4963:doi
4959:174
4922:PMC
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