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agonists generally produce a dysphoric state. Morphine, a MOR agonist, was one of the earliest studied drugs at the advent of ICSS and BSR. High potency MOR agonists like morphine have a somewhat varied effect on ICSS responding despite having high abuse potential, resulting in both potentiation and depression. The effect these drugs have on ICSS responding has been found to be highly dependent on dose, pretreatment time, and previous opioid exposure. Various studies on the effect of MOR-selective drugs including morphine, heroin, fentanyl, methadone, and hydrocodone have found mixed effects on ICSS responding. Low doses of these drugs have been found to elicit weak facilitation of ICSS, while high doses result in a biphasic ICSS profile, consisting of a higher threshold for ICSS at lower frequencies followed by ICSS potentiation at higher frequencies. Upon chronic administration of high-potency MOR agonists at low doses, there is no tolerance to ICSS facilitation.
561:, can reverse the effects of both opioid receptor agonists on ICSS responding and the potentiating effects of psychostimulants like methamphetamine. Naloxone, which is a competitive antagonist of all opioid receptor sub-types, does not influence ICSS responding when administered on its own. KOR agonism, typically associated with dysphoric states, more consistently results in a depression of ICSS responding. The KOR agonist salvinorin-A, for example, causes an overall decrease in ICSS response rates at lower stimulation frequencies. Repeated administration does not produce tolerance to ICSS depression. The effects of delta opioid receptor (DOR) agonists/antagonists on ICSS are less clear. One DOR agonist, SNC80, has been found to cause ICSS depression, but there is counter-evidence suggesting some delta agonists might have weak ICSS facilitation properties.
541:), tend to be less addictive, and they have mixed effects on ICSS responding depending on dose and stimulation frequency. Serotonin selective drugs, however, tend to result in either a lack of ICSS potentiation or depression of ICSS responding (a right-shift in frequency-rate curve), and these drugs are generally considered to be less addictive. One such example is fenfluramine, which was previously marketed as an appetite suppressant. Dopamine antagonists generally result in the depression of ICSS responding and a rightward-shift in the frequency-rate curve. This suggests decreased BSR and possibly increased aversive properties of the stimulation. Following chronic treatment with a dopamine antagonist, there is withdrawal-induced facilitation of ICSS, the opposite effect of what is observed following chronic treatment with stimulants.
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Following FR1 training, it is typical to establish a minimum, threshold current that produces sufficient levels of ICSS responding (about 40 responses per minute). This is called a discrete-trial current intensity procedure. Each discrete trial consists of non-contingent stimulation at a certain amplitude followed by a brief window during which the animal can respond for more stimulation. Effective currents for BSR elicit responding above a certain rate (3 out of 4 trials, for example). The lowest current the animal responds sufficiently to is deemed the minimum effective current. This is done at a constant frequency, typically at the higher end of the frequency range employed in ICSS studies (140â160 Hz).
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drug, is examined. This method allows for quantitative analysis of reward-modulating treatments on response rates in comparison to baseline conditions. Lower stimulation frequencies fail to sustain ICSS responding at a probability above chance. Response rates increase rapidly over a dynamic range of stimulation frequencies as the frequency increases, until a maximum response rate is reached. Changes in the rate of response over this range reflects changes in the magnitude of the reward. Rate-frequency, rate-intensity, or rate-duration functions make inferences about the potency and efficacy of stimulation, as well as elucidate how drugs alter the rewarding impact of stimulation.
70:) is the operant conditioning method used to produce BSR in an experimental setting. ICSS typically involves subjects with permanent electrode implants in one of several regions of the brain known to produce BSR when stimulated. Subjects are trained to continuously respond to electrical stimulation of that brain region. ICSS studies have been particularly useful for examining the effects of various pharmacological manipulations on reward sensitivity. ICSS has been utilized as a means to gauge addiction liability for drugs of many classes, including those that act on monoaminergic, opioid, and cholinergic neurotransmission. These data correlate well with findings from
90:, observed that rats preferred to return to the region of the test apparatus where they received direct electrical stimulation to the septal area of the brain. From this demonstration, Olds and Milner inferred that the stimulation was rewarding, and through subsequent experiments, they confirmed that they could train rats to execute novel behaviors, such as lever pressing, in order to receive short pulse trains of brain stimulation. Olds and Milner discovered the reward mechanisms in the brain involved in positive reinforcement, and their experiments led to the conclusion that electrical stimulation could serve as an operant reinforcer. According to
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stimulation has a highly compulsive component characteristic of an addicted state. BSR is hypothesized to be so effective in establishing compulsive habits due to its more direct activation of the reward pathway, bypassing transmission through sensory pathways in response to natural rewards. Delayed reinforcement following a response for BSR decreases how strongly this behavior is reinforced and to what extent it continues. A delay of one second, for example, between a lever-press and reward delivery (stimulation) can reduce response levels. BSR offers insights into the neural circuitry involved in reinforcement and compulsive behavior.
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the frequency-rate curve and sensitization of the reward circuitry to stimulation. An increase in the M50 indicates that a greater stimulation frequency was required to reach 50% of the MCR, and the reward circuitry has been desensitized by the experimental manipulation. Another way of analyzing the frequency-rate curve between control and experimental conditions is to do a linear regression through the ascending data points in a plot of raw data (which has not been normalized to the MCR). The point where y=0, or the x-intercept, is called the threshold frequency or theta zero (Ξ
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specifically, the number of responses for any given trial is divided by the highest number of responses recorded in a baseline condition trial, which is then multiplied by 100. In an experimental condition, if the MCR falls below 100% at the highest stimulation frequencies, it is thought to reflect an impacted capability or motivation to respond, potentially induced by a drug with sedative or aversive properties. Shifts above 100% of the MCR indicate improved ability or motivation to respond, potentially induced by a drug with rewarding or stimulant properties.
624:. Low doses of these drugs generally result in ICSS facilitation, while higher doses can result in depression of ICSS and an overall decrease in the maximum response rate. The latter is likely related to an impaired ability to respond due to the sedative and hypnotic properties of these drugs. Ethanol influences GABA receptor activity, and has been found to moderately facilitate ICSS, despite older publications suggesting these findings are inconsistent.
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neurotransmitter systems. Pharmacological manipulation of these systems can have either a direct or indirect effect on the activity of the reward circuitry. Understanding drug-specific effects on ICSS response thresholds has helped elucidate how different neurotransmitter systems influence the reward circuitry by either potentiating or suppressing sensitivity to rewarding stimulation and influencing motivation to perform reward-associated behaviors.
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baseline, and there is a significant response rate at the lowest frequency, which did not produce responding under baseline conditions. Even following chronic administration of methamphetamine or cocaine, there is little to no tolerance to ICSS facilitation. After chronic treatment is stopped, however, there is a withdrawal-induced depression of ICSS responding, which can be reversed by re-administering the drug.
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experiments have been criticized as "dubious and precarious (even) by yesterday's standards". In a case published in 1986, a subject who was given the ability to self-stimulate at home ended up ignoring her family and personal hygiene, and spent entire days on electrical self-stimulation. By the time her family intervened, the subject had developed an open sore on her finger from repeatedly adjusting the current.
361:. In ICSS studies using mice, a response wheel is usually used instead of a lever, as mice do not consistently perform lever-pressing behaviors. Each quarter turn of the response wheel is recorded and rewarded with stimulation. The rewarding stimulus in BSR experiments is typically a train of short-duration pulses separated by interval pulses, which can be manipulated experimentally using the
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assess the abuse liability of various future therapeutics. Additionally, ICSS studies have potential to be used to gauge how reward sensitivity is affected by genetic factors associated with addictive disorders. Drugs found to prevent ICSS facilitation have potential to be developed and therapeutically implemented to reduce the risk of addictive disorders in a clinical setting.
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depressive effects of high doses. Withdrawal-induced depression of ICSS facilitation at low doses is also observed, as in MOR agonists and monoamine stimulants. The effects of nicotine treatment on ICSS response thresholds and maximum response rates are not as significant as they are in the case of many addictive MOR agonists and monoamine stimulants.
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implementing a progressive-ratio schedule, where the number of required responses continually increases. The number of required responses increases for each trial until the animal fails to reach the required number of responses. This is considered the "break-point" and is a good indication of motivation related to reward magnitude.
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notably lacks an established neural representation in memory that naturally facilitates the learning of reward expectancy. Both of these effects lead to diminished response rate for BSR in the early trials of a series; however, experiments have also shown that extinguished behavior can be quickly reinstated by a
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While the amplitude of the stimulation influences which neurons are stimulated, the frequency of stimulation determines the firing rate induced in that neuronal population. Generally, increasing stimulation frequency increases the firing rate in the target population. This is associated with higher
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is a portion of the hypothalamus, and brain stimulation to this area at the level of the medial forebrain bundle produces the highest response rates and subsequently the highest reward potency in rodents. Lesions in this region or along its boundary cause a loss of positive drive-reward behaviors as
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Investigation of the brain reward circuitry reveals that it consists of a distributed, multi-synaptic circuit that determines both BSR and natural reward function. The natural drives that motivate and shape behavior reach the reward circuitry trans-synaptically through the peripheral senses of sight,
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The first portion of an ICSS experiment involves training subjects to respond for stimulation using a fixed-ratio 1 (FR-1) reinforcement schedule (1 response = 1 reward). In experiments involving rats, subjects are trained to press a lever for stimulation, and the rate of lever-pressing is typically
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Sensitivity of the neural circuitry to the rewarding properties of stimulation is assessed by analyzing left- or right-shifts in the M50, or the frequency at which 50% of the maximum number of responses was recorded. Reaching 50% of the MCR at a lower frequency is characteristic of a left-shift in
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stimulation amplitudes. This corrective process is limited, however, since increasing the population of activated neurons can result in off-target activation of neighboring circuitry. This is often culminated in undesired motor side effects upon stimulation, due to the adjacency of the MFB to the
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Mapping and lesion studies on BSR were designed to determine the location of reward-relevant neurons as well as determine the signal pathways that are directly affected by brain stimulation. The site of intracranial self-stimulation leads to substantially different behavioral characteristics. Sites
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Satiation experiments in rats have revealed that BSR does not produce satiety. Olds demonstrated that this lack of satiation associated with BSR allows animals to self-stimulate to sheer exhaustion and that satiation is dependent on the location of the electrical stimulation. In a 48-hour satiation
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Natural rewards are associated with a state of deprivation from unmet needs or desires (e.g., hunger). These states drive instinctual, motivated behaviors like food consumption. It has been argued that this is not the case with BSR, as it does not meet an intrinsic survival-based need. BSR also
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have been studied extensively in relation to BSR. Neurochemical studies have shown that BSR results in the release of dopamine within the nucleus accumbens. This effect is generally potentiated following administration of drugs that themselves increase the amount of extracellular dopamine in the
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Stimulation intensity, pulse duration, or pulse frequency can be varied to determine dose-response functions ICSS responding using curve-shift analysis. This approach generally resembles traditional pharmacological dose-response curve where the frequency of stimulation, rather than the dose of a
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Since the initial demonstration of BSR by Olds and Milner, experiments in rodents record ICSS responding to quantify motivation to receive stimulation. Subjects undergo stereotaxic surgery to permanently implant either a monopolar or bipolar electrode to the desired brain region. Electrodes are
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dopamine system in motivational function. The motivational effect of intracranial self-stimulation varies substantially depending on the placement site of the surgically implanted electrode during electrical stimulation, and animals will work to stimulate different neural sites depending on their
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sub-type of nicotinic receptors. Many studies have confirmed that low doses of nicotine result in ICSS facilitation, while higher doses result in ICSS depression. Chronic treatment with nicotine does not result in tolerance to ICSS facilitation at low doses, but does result in tolerance to the
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system generally vary in selectivity for the mu (ÎŒ), delta (ÎŽ), and kappa (Îș) opioid receptors. Their addictive properties are highly dependent on these selectivities. Generally speaking, high potency mu-opioid receptor (MOR) agonists have high abuse potential, while kappa-opioid receptor (KOR)
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indicating sensitization of the reward circuitry and high abuse potential. This characteristic leftward-shift of M50 in response to a moderate dose of cocaine is illustrated in a hypothetical data set in Figure 1. Note that the maximum response rate is reached at a lower frequency than it is at
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of the neurotransmitter. While dopamine is generally considered to be the main neurotransmitter implicated in the reward system, it is often not the only neurotransmitter affected by addictive, monoaminergic drugs. Importantly, the circuitry involved in BSR is multi-synaptic and not exclusively
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Example frequency-rate plot for 10 trials over increasing stimulation frequencies. Hypothetical data (which reflects established concepts in ICSS procedures) is plotted as the percent maximum responses for any given trial during a sequence. The blue line represents hypothetical data at baseline,
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At a constant minimum effective current, ICSS responding is recorded over a series of trials, which vary in stimulation frequency. Each trial consists of a short priming phase of non-contingent stimulation, a response phase where responses are recorded and rewarded with stimulation, and a short
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electrodes showed radical slowing of self-stimulation after 4 to 8 hours. The insatiability of BSR is closely related to the strength of drive. While a natural reward, like food, is met with a feeling of being full (satiety), BSR does not have a comparable correlate. This allows for BSR to be
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Mechanisms of BSR offer a tool that provides insight into the way the brain governs behavior through motivation and reinforcement, especially in regard to addictive and compulsive behaviors. ICSS studies of BSR have proven to be a robust measure of reward sensitivity, and have potential to help
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verification of electrode placement to ensure consistency between experimental groups. Subjects with imperfect electrode placement require a higher simulation amplitude to activate the reward circuitry and produce ICSS responding. Subjects with ideal anatomical placement will respond at lower
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The relationship between BSR and natural rewards (e.g. food, water and copulation) has long been debated, and much of the early research on BSR is focused on their respective similarities and differences. BSR is facilitated through the same reinforcement pathway activated by natural rewards.
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In one oft-cited example, in 1972, Heath's subject known as "B-19" reported "feelings of pleasure, alertness, and warmth" and "protested each time the unit was taken from him, pleading to self-stimulate just a few more times". Among ethicists, early "direct brain stimulation" or "psychosurgery"
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The amplitude (current) of stimulation determines the population of neurons being activated by the implanted electrode. In certain approaches, this is adjusted for every subject due to minor variability in electrode placement, and therefore a slightly different population of affected neurons.
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stimulation that refreshes the short-term association involved in reward expectancy. Studies on BSR indicate that reinforcing brain stimulation may activate the natural pathways associated with natural drives as well as stimulate the reinforcement pathways that are usually activated by natural
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have been shown to work in a compulsive manner to receive intravenous injections of stimulants, and when access to the drugs is not limited, they will self-administer drugs to the point of severe weight loss and death. Similar to self-administration behavior, responding for intracranial brain
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properties generally increase the stimulation threshold to achieve ICSS responding. These studies provide insight into the specific neurochemical mechanisms involved in the facilitation of BSR, and how reward perception can be modulated by pharmacologically altering the activity of specific
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Addiction is a chronic brain disorder consisting of compulsive drug-taking and seeking that is maintained despite detrimental effects on various aspects of life including health, relationships, and work. Laboratory procedures can establish compulsive self-administration habits of seeking and
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Additionally, drugs that affect monoamine transmission vary in their selectivity. For example, drugs with high selectivity for increasing dopamine and norepinephrine transmission relative to serotonin transmission tend to have highly addictive properties. Amphetamine and cocaine share this
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Curve-shift analysis is often used in pharmacological studies to compare baseline response rates to those following drug administration. The maximum response rate during baseline conditions is typically used to normalize data in a frequency-rate curve to a maximum control rate (MCR). More
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The independent variables of stimulation train and pulse duration can also be varied to determine how each affects ICSS response rates. Longer train durations produce more vigorous responding up to a point, after which rate of responding varies inversely with train length. This is due to
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The reinforcement schedule can also be manipulated to determine how motivated an animal is to receive stimulation, reflected by how hard they are willing to work to earn it. This can be done by increasing the number of responses required to receive a reward (FR-2, FR-3, FR-4, etc.) or by
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Several major drug classes have been studied extensively in relation to ICSS behavior: monoaminergic drugs, opioids, cholinergic drugs, GABAergic drugs, as well as a small number of drugs from other classes. These studies generally compare ICSS responding at baseline and following drug
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sound, taste, smell, or touch. However, experimentally-induced BSR more directly activates the reward circuitry and bypasses transduction through peripheral sensory pathways. For this reason, electrical brain stimulation provides a tool for identifying the reward circuitry within the
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while the black line represents hypothetical data following administration of 10 mg/kg cocaine to the subject. This reflects the characteristic "left-shift" of the frequency-rate curve following administration of a drug that increases dopaminergic transmission in the reward pathway.
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and intracranial drug injections produce robust reward sensation due to a relatively direct activation of the reward circuitry. This activation is considered to be more direct than rewards produced by natural stimuli, as those signals generally travel through the more indirect
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of the mesolimbic dopamine system, a key component of the reward circuitry, generally have high thresholds for stimulation. However, these thresholds can be increased or decreased by drug administration, influencing sensitivity to intracranial stimulation and ICSS behavior.
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and reinforcement to be understood in terms of their underlying physiology, and it led to further experimentation to determine the neural basis of reward and reinforcement. Since the initial discovery, the phenomenon of BSR has been demonstrated in all species tested, and
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nerves. BSR has been found in all vertebrates tested, including humans, and it has provided a useful tool for understanding how natural rewards are processed by specific brain regions and circuits, as well the neurotransmission associated with the reward system.
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when both food and stimulation are offered concurrently for a limited time each day. Rats will also cross electrified grids to press a lever, and they are willing to withstand higher levels of shock to obtain electrical stimulation than to obtain food.
181:. Multiple studies have demonstrated that rats will perform reinforced behaviors at the exclusion of all other behaviors. Experiments have shown rats will forgo food to the point of starvation in exchange for brain stimulation or intravenous
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time-out phase where responses are not recorded and no stimulation is delivered. This is repeated for a series of 10-15 different ascending or descending frequencies, in 0.05 log-unit increments, which range anywhere from 20 to 200 Hz.
520:. Conversely, these levels are decreased and the rewarding properties of BSR are blocked following administration of drugs that antagonize dopamine receptors or reduce the amount of extracellular dopamine, by promoting either degradation or
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BSR and drugs of addiction produce their rewarding effects through shared neuroanatomical and neurochemical mechanisms. Studies using lesion, pharmacological, and anatomical mapping of the brain have revealed that many drugs of abuse (e.g.
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with some degree of anatomical and neurochemical specificity. Studies involving these two forms of laboratory reward showed stimulation of a broad range of limbic and diencephalic structures could be rewarding as well as implicated the
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have been found to result in ICSS depression and have been found to inhibit the reinforcing effects of several drugs, including cocaine, methamphetamine, and nicotine, reversing the ICSS facilitation these drugs typically cause.
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Kokarovtseva L, Jaciw-Zurakiwsky T, Mendizabal
Arbocco R, Frantseva MV, Perez Velazquez JL (2009). "Excitability and gap junction-mediated mechanisms in nucleus accumbens regulate self-stimulation reward in rats".
280:. MFB is not the sole anatomical substrate responsible for reinforcing brain stimulation; however, it is the main tract for the ascending dopamine fibers, and it functions to relay information from the VTA to the
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and limbic brain structures to mediate behaviors the reinforce reward. It is a major target for the dopaminergic projections from the VTA, a group of neurons located close to the midline on the floor of the
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data suggest stimulation of the MFB or VTA does not directly activate dopaminergic neurons in the mesolimbic reward pathway. These data suggest BSR is facilitated by initial excitation of descending,
94:, operant reinforcement occurs when a behavior is followed by the presentation of a stimulus, and it is considered essential to the learning of response habits. Their discovery enabled
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Chiamulera C, Padovani L, Corsi M (August 2017). "Drug discovery for the treatment of substance use disorders: novel targets, repurposing, and the need for new paradigms".
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Within-subject study design is often implemented to help eliminate variability introduced by electrode placement. Between-subject study design requires rigorous
156:(MFB) through either electrical or chemical means activates key components of the reward pathway also activated by natural rewards. When specific regions of the
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inputs to the VTA are thought to play a role in this indirect activation, but the neuroanatomical components of this circuit have yet to be fully characterized.
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BSR has been shown to result in the release of dopamine within the nucleus accumbens, which also occurs in response to natural rewards such as food or sex.
577:(nAchRs), which are ligand-gated ion channels. The addictive properties of nicotine have been found to be associated with agonism specifically of the
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dopaminergic. This introduces potential for modulation by other neurotransmitter systems at different stages in the transmission of the reward signal.
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Self-stimulation can exert robust activation of central reward mechanisms due to more direct action than natural rewards, which initially activate
441:). This is the frequency at which ICSS response rates are equal to 0 (and any frequency above this will theoretically elicit ICSS responding).
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Choi HD, Shin WG (April 2016). "Meta-analysis of the association between a serotonin transporter 5-HTTLPR polymorphism and smoking cessation".
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Rats will perform lever-pressing at rates of several thousand responses per hour for days in exchange for direct electrical stimulation of the
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Phillips AG, Blaha CD, Fibiger HC (1989). "Neurochemical correlates of brain-stimulation reward measured by ex vivo and in vivo analyses".
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Marcus R, Kornetsky C (March 1974). "Negative and positive intracranial reinforcement tresholds [sic] : Effects of morphine".
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Drugs with more balanced selectivity for dopamine/norepinephrine and serotonin transmission, such as 3,4-methylenedioxy-methamphetamine (
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Bauzo RM, Bruijnzeel AW (2012). "Animal models of nicotine withdrawal: intracranial self-stimulation and somatic signs of withdrawal".
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Sonnenschein B, Conover K, Shizgal P (2003). "Growth of brain stimulation reward as a function of duration and stimulation strength".
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ICSS response rates, eventually reaching a maximum level at the maximum firing rate, limited by the refractory properties of neurons.
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Liebman JM (1983). "Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology".
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Olds J, Milner P (1954). "Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain".
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268:(MFB) is the location of the most frequently investigated brain stimulation reward sites, and it is composed of a complex bundle of
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Cholinergic drugs have been less extensively studied than monoamines and opioids. The most commonly studied cholinergic drug is
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Bozarth MA, Wise RA (1985). "Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat".
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616:, and they are commonly prescribed for therapeutic uses. Several of these drugs have addictive properties, including several
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Carlezon WA, Chartoff EH (2007). "Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation".
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Drugs with increased addiction liability generally decrease the stimulation threshold for ICSS responding, while drugs with
50:, along with other regions of the brain associated with natural reward, was both rewarding as well as motivation-inducing.
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Olds J, Travis RP (April 1960). "Effects of chlorpromazine, meprobamate, pentobarbital and morphine on self-stimulation".
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receptors, which are ligand-gated ion channels, are more widely studied, as they generally produce more robust effects on
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1978:"Converging findings from linkage and association analyses on susceptibility genes for smoking and other addictions"
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are electrically stimulated, it elicits reward-related behaviors such as eating, drinking, or copulation responses.
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current state. Often, animals that work to initiate brain stimulation will also work to terminate the stimulation.
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284:. The rewarding effect of MFB stimulation is mediated via the activation of the mesocorticolimbic dopamine system.
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Barr AM, Markou A, Phillips AG (2002). "A 'crash' course on psychostimulant withdrawal as a model of depression".
481:, etc.) activate the reward circuitry of the MFB, which is similarly activated by stimulation to achieve BSR. The
394:. Inadvertent stimulation of these axons can lead to motor output such as movement of the head or paw twitching.
26:) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by
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Kornetsky C, Bain GT, Unterwald EM, Lewis MJ (October 1988). "Brain stimulation reward: effects of ethanol".
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selectivity profile, and administration of these drugs generally results in a left-shift in M50 and Ξ
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administration. Typically, the frequency-rate approach is used to determine changes in the M50 or Ξ
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Nihon
Arukoru Yakubutsu Igakkai Zasshi = Japanese Journal of Alcohol Studies & Drug Dependence
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Early studies on the motivational effects of brain stimulation addressed two primary questions:
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Phillips TJ, Reed C (November 2014). "Targeting GABAB receptors for anti-abuse drug discovery".
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electrodes self-stimulated to exhaustion and showed no intrinsic satiation tendencies, whereas
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lever-pressing for additional stimulation before the previously earned train has finished.
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neurons, which then activate the ascending, unmyelinated neurons of the VTA. Excitatory,
573:, the highly-addictive, psychoactive substance in cigarettes. Nicotine is an agonist of
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Esposito RU, Kornetsky C (June 1978). "Opioids and rewarding brain stimulation".
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1. Which brain sites can be stimulated to produce the perception of reward? and
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Pleasurable phenomenon elicited via direct stimulation of specific brain regions
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GABAergic transmission is inhibitory, and the two main receptors for GABA are
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2. Which drugs influence the response to stimulation and via what mechanism?
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2117:: Targeting Misbehaving Brain Circuitry with Therapies like ECT, DBS, and TMS
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Substance Use Disorders".
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983:"Intracranial self-stimulation to evaluate abuse potential of drugs"
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connected to a stimulating apparatus at the time of the experiment.
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experienced indefinitely, or in the case of ICSS, until exhaustion.
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Vlachou S, Markou A (2010). "GABAB receptors in reward processes".
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390:, a bundle of axons carrying descending motor information to the
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cell bodies that comprise the mesocorticolimbic dopamine system.
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are associated with the strongest reward effects of stimulation.
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538:
366:
240:
42:
and establishes response habits similar to those established by
503:
The effects of drugs that alter neurotransmission of dopamine,
2115:
Brain
Stimulation: Can Magnetic or Electrical Pulses Help You?
1250:"Can Electrically Stimulating Your Brain Make You Too Happy?"
493:
1904:. Advances in Pharmacology. Vol. 58. pp. 315â71.
782:"Brain reward circuitry: insights from unsensed incentives"
213:
ingesting that qualify as addictive behaviors. Rodents and
103:
similarly demonstrated that BSR can be applied to humans.
1943:
Child and
Adolescent Psychiatric Clinics of North America
1748:
Melroy-Greif WE, Stitzel JA, Ehringer MA (January 2016).
1645:
The
Journal of Pharmacology and Experimental Therapeutics
1079:
Milner PM (1991). "Brain-stimulation reward: a review".
832:
Wise RA, Rompre PP (1989). "Brain dopamine and reward".
2123:: Neurosurgical Treatments Using Deep Brain Stimulation
1902:
1030:
1028:
1026:
1037:
2129:: Drugs, Brain, Behavior- The Science of Addiction
1173:Berridge, K. C. (2003). "Pleasures of the brain".
300:. The nucleus accumbens is located in the ventral
1797:Itasaka M, Hironaka N, Miyata H (June 2015). "".
1436:
1434:
1517:
1515:
906:
904:
902:
900:
898:
896:
894:
892:
890:
365:of stimulation amplitude, frequency, and pulse
343:Intracranial self-stimulation (ICSS) procedures
38:reinforcer. Targeted stimulation activates the
1867:Alcoholism: Clinical and Experimental Research
74:studies on the addictive properties of drugs.
1074:
1072:
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8:
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725:
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717:
715:
1119:Olds J (1975). "Reward and Drive Neurons".
1114:
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256:well as all other operant drive behaviors.
1234:10.1001/virtualmentor.2015.17.1.oped2-1501
143:Relationship to natural rewards and drives
2001:
1773:
1232:
1006:
797:
1672:Neuroscience & Biobehavioral Reviews
231:(MFB) through the lateral and posterior
691:
1707:Neuroscience and Biobehavioral Reviews
1567:Neuroscience and Biobehavioral Reviews
1524:Neuroscience and Biobehavioral Reviews
373:Establishing minimum effective current
557:Opioid receptor antagonists, such as
7:
846:10.1146/annurev.ps.40.020189.001203
744:10.1146/annurev.ne.19.030196.001535
1879:10.1111/j.1530-0277.1988.tb00250.x
1610:Trends in Pharmacological Sciences
1374:10.1016/j.neuroscience.2009.01.065
1140:The American Journal of Psychiatry
640:Clinical and pre-clinical evidence
14:
981:Negus SS, Miller LL (July 2014).
575:nicotinic acetylcholine receptors
1443:Expert Opinion on Drug Discovery
1338:10.1001/jama.1985.03360010087032
1217:"The New Era of Neuromodulation"
304:and integrates information from
2070:Current Opinion in Pharmacology
111:Brain stimulation reinforcement
1081:Canadian Journal of Psychology
633:positive allosteric modulators
1:
1976:Yang J, Li MD (August 2016).
1910:10.1016/S1054-3589(10)58013-X
1719:10.1016/s0149-7634(88)80068-x
1622:10.1016/S0165-6147(02)02086-2
1579:10.1016/S0149-7634(89)80017-X
1248:Frank, Lone (21 March 2018).
1187:10.1016/S0278-2626(03)00014-9
799:10.1016/s0896-6273(02)00965-0
732:Annual Review of Neuroscience
64:Intracranial self-stimulation
34:. BSR can serve as a robust
2039:10.1097/YPG.0000000000000116
1834:10.1007/978-1-61779-458-2_16
1684:10.1016/0149-7634(78)90052-0
1536:10.1016/0149-7634(83)90007-6
1455:10.1517/17460441.2014.956076
1295:10.1126/science.127.3294.315
1227:(1): 74â81. 1 January 2015.
881:10.1016/0301-0082(74)90005-7
313:. The VTA is the origin of
52:Electrical brain stimulation
1417:10.1037/0735-7044.117.5.978
834:Annual Review of Psychology
512:nucleus accumbens, such as
134:-containing neurons of the
2164:
2082:10.1016/j.coph.2017.08.009
680:Wirehead (science fiction)
272:projecting from the basal
1955:10.1016/j.chc.2016.02.002
1754:Genes, Brain and Behavior
604:. Drugs that act on GABA
398:Frequency-rate responding
1121:Brain Stimulation Reward
869:Progress in Neurobiology
780:Wise RA (October 2002).
296:connects the VTA to the
227:along the length of the
20:Brain stimulation reward
1405:Behavioral Neuroscience
987:Pharmacological Reviews
266:medial forebrain bundle
260:Medial forebrain bundle
229:medial forebrain bundle
154:medial forebrain bundle
40:reward system circuitry
2121:Deep Brain Stimulation
925:10.1038/nprot.2007.441
665:Deep brain stimulation
660:Affective neuroscience
631:receptor agonists and
549:Drugs that act on the
500:
237:ventral tegmental area
127:central nervous system
101:Robert Galbraith Heath
1826:Psychiatric Disorders
1221:AMA Journal of Ethics
1152:10.1176/ajp.120.6.571
999:10.1124/pr.112.007419
497:
445:Modulation with drugs
363:independent variables
86:and Peter Milner, of
2027:Psychiatric Genetics
1982:Molecular Psychiatry
424:Curve-shift analysis
329:Electrophysiological
253:lateral hypothalamus
247:Lateral hypothalamus
239:(VTA), and into the
179:lateral hypothalamus
48:lateral hypothalamus
2127:Drugs and The Brain
1486:Psychopharmacologia
1175:Brain and Cognition
490:Monoaminergic drugs
324:Indirect activation
72:self-administration
1994:10.1038/mp.2016.67
1498:10.1007/BF00421282
670:Experience machine
501:
359:dependent variable
294:mesolimbic pathway
288:Mesolimbic pathway
215:non-human primates
1843:978-1-61779-457-5
1766:10.1111/gbb.12251
565:Cholinergic drugs
298:nucleus accumbens
282:nucleus accumbens
222:Anatomy of reward
173:Strength of drive
150:peripheral nerves
88:McGill University
2155:
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348:Initial training
276:regions and the
195:test, rats with
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1362:Neuroscience
1361:
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1257:. Retrieved
1254:The Atlantic
1253:
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1146:(6): 571â7.
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158:hypothalamus
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92:B.F. Skinner
81:
67:
63:
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32:Peter Milner
23:
19:
18:
2076:: 120â124.
1713:(1): 1â17.
1651:: 397â404.
1492:(1): 1â13.
1332:(1): 81â3.
1259:19 February
1087:(1): 1â36.
840:: 191â225.
518:transporter
467:amphetamine
337:cholinergic
2143:Perception
2137:Categories
738:: 319â40.
686:References
383:histologic
333:myelinated
136:mesolimbic
96:motivation
84:James Olds
57:peripheral
28:James Olds
2148:Addiction
655:Addiction
522:re-uptake
509:serotonin
392:brainstem
274:olfactory
208:Addiction
190:Satiation
169:rewards.
82:In 1953,
2090:28874314
2055:23494040
2047:26886943
2012:27166759
1963:27338962
1928:20655488
1852:22231819
1811:26502572
1784:26351737
1692:54232959
1657:14428622
1630:12368072
1595:11772466
1552:26513856
1506:45059299
1463:25195620
1425:14570548
1390:12059974
1382:19409225
1303:13506579
1195:12812810
1160:14086435
1057:13233369
1017:24973197
941:13085385
933:18007634
808:12383779
649:See also
610:sedation
571:nicotine
559:naloxone
479:nicotine
458:aversive
367:duration
311:midbrain
306:cortical
302:striatum
132:dopamine
2098:3413116
2003:4956568
1887:2852475
1775:4780670
1735:1075158
1727:3287237
1587:2530478
1544:6132357
1471:2310286
1346:4039767
1311:6411230
1283:Science
1203:6640313
1127:: 1â30.
1101:2044020
1008:4081730
854:2648975
752:8833446
614:anxiety
545:Opioids
514:cocaine
475:opioids
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