491:. The male but not female offspring of these cocaine-exposed rats inherited both epigenetic marks (i.e., di-acetylation of lysine residues 9 and 14 on histone 3) within mPFC neurons, the corresponding increase in BDNF expression within mPFC neurons, and the behavioral phenotype associated with these effects (i.e., a reduction in cocaine reward, resulting in reduced cocaine-seeking by these male offspring). Consequently, the transmission of these two cocaine-induced epigenetic alterations (i.e., H3K9ac2 and H3K14ac2) in rats from male fathers to male offspring served to reduce the offspring's risk of developing an addiction to cocaine. As of 2018, neither the heritability of these epigenetic marks in humans nor the behavioral effects of the marks within human mPFC neurons has been established.
579:
that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
715:
al., 1972). The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse. ... The evidence presented here demonstrates that rapid environmental adaptation occurs following exposure to a number of stimuli. Epigenetic mechanisms represent the key components by which the environment can influence genetics, and they provide the missing link between genetic heritability and environmental influences on the behavioral and physiological phenotypes of the offspring.
194:(inheritable traits) risk factors to the total risk is unknown. Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time (e.g., weeks–months) can result in an addiction. In other words, anyone can become an individual with a substance use disorder under particular circumstances. Research is working toward establishing a comprehensive picture of the neurobiology of addiction vulnerability, including all factors at work in propensity for addiction.
417:, certain addiction-induced epigenetic alterations in rats can be transmitted from parent to offspring and produce behavioral phenotypes that decrease the offspring's risk of developing an addiction. More generally, the heritable behavioral phenotypes that are derived from addiction-induced epigenetic alterations and transmitted from parent to offspring may serve to either increase or decrease the offspring's risk of developing an addiction.
274:
A major environmental factor that increases vulnerability to developing addiction is availability of drugs. Additionally, socioeconomic status and poor familial relationships have been shown to be contributing factors in the initiation and continued use of alcohol or other drugs. Neurobiology plays a
239:
receptor responds to the chemical dopamine which produces rewarding and pleasurable feelings in the brain. Through mice studies, agreeing contemporary research has shown that individuals with a deficiency in this dopamine receptor exhibit not only a preference for and increased consumption of alcohol
634:
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification
631:
Substance-use disorder: A diagnostic term in the fifth edition of the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to
324:
Although many variables individually contribute to an increased risk of developing a substance use disorder, no single vulnerability guarantees the development of addiction. It is the combination of many factors (e.g. genetics, environmental stressors, initiation and continued use of the drug) that
307:
In other words, repeated, deliberate use of the drug plays a role in the eventual compulsory drug-taking and/or habitual drug-taking associated with addiction. Another theory suggests that through repeated use of the drug, individuals become sensitized to drug-associated stimuli which may result in
294:
produced by the stressors. Evidence has also shown that a great amount of stress hinders prefrontal functioning and causes an increased limbic-striatal level response. This can lead to low behavioral and cognitive control. Additionally, when the brain is put under severe stress due to repeated drug
345:
of the brain undergoes reorganization and functional changes during adolescence. Rat studies have shown that adolescents have tendencies and abilities to drink more than adults due to minimal disruption to their motor functions and minimal sensitivity to sedation. As a result, adolescents are more
193:
during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction; the contribution from epigenetic
714:
However, the components that are responsible for the heritability of characteristics that make an individual more susceptible to drug addiction in humans remain largely unknown given that patterns of inheritance cannot be explained by simple genetic mechanisms (Cloninger et al., 1981; Schuckit et
578:
Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use,
265:
Additionally, genetics play a role on individual traits, which may put one at increased risk for experimentation with drugs, continued use of drugs, addictions, and potential for relapse. Some of these individual personality traits, such as impulsivity, reward-seeking, and response to stress, may
261:
dopamine receptor may be more likely to seek out these recreational pleasure/reward producing substances as they are less receptive to the natural “feel good’’ effects of dopamine. This naturally occurring deficiency is one of the most studied genetic vulnerabilities to substance abuse across the
202:
Accepted research now shows that some people have vulnerabilities to addiction and has established a three-factor standard for vulnerability to drug addiction: genetic factors, environmental factors, and repeated exposure to drugs of use. Being vulnerable to addiction means there is a factor that
303:
Repeated exposure to a drug is one of the determining factors in distinguishing recreational substance use from chronic abuse. Many neurobiological theories of addiction place repeated or continued use of the drug in the path of addiction development. For example, researchers have theorized that
333:
Previous research has examined the increased risk of early-onset substance use during adolescence. Many factors have been identified as being associated with increased risk of substance use during this period of development including individual differences (e.g., negative affect, decreased harm
334:
avoidance, and low motivation for achievement), biological (e.g., genetic predisposition and neurological development), and environmental factors (e.g., high levels of stress, peer influences, availability of substances, etc.) Rat studies provide behavioral evidence that
320:
is a hallmark of repeated drug exposure and refers to the adaptation of the brain due to increased levels of the drug in the body. In this sense, repeated exposure falls under both physiological vulnerability and behavioral/psychological vulnerability to addiction.
311:
Additionally, a third neurobiological theory highlights the changes in brain reward circuitry following repeated drug use that contributes to the development of addiction such that addiction is conceptualized as being a progression of
384:
which arise through chronic exposure to addictive stimuli during an addiction can be transmitted across generations, in turn affecting the behavior of one's children (e.g., the child's behavioral responses to addictive drugs and
412:
epigenetic alterations that arise from various forms of addiction in humans and the corresponding behavioral phenotypes from these epigenetic alterations that occur in human offspring. Based upon preclinical evidence from
1456:
Thomas, Mark J.; Beurrier, Corinne; Bonci, Antonello; Malenka, Robert C. (5 November 2001). "Long-term depression in the nucleus accumbens: A neural correlate of behavioral sensitization to cocaine".
262:
field. Recent studies show that GABA also plays a role in vulnerability to addiction. When alcohol is consumed it affects GABA by mimicking its effects on the brain, such as basic motor functions.
368:
genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual; they also serve as the mechanism responsible for
223:
as a major contributing factor to addiction vulnerability. It has been estimated that 40–60% of the vulnerability to developing an addiction is due to genetics. One gene in particular, the
1062:
Kreek, M. J.; Nielsen, D. A.; Butelman, E. R.; Laforge, K. S. (2005). "Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction".
1534:
Nation, M.; Heflinger, C. A. (2006). "Risk
Factors for Serious Alcohol and Drug Use: The Role of Psychosocial Variables in Predicting the Frequency of Substance Use Among Adolescents".
346:
susceptible to developing substance used disorders. The social, behavioral, and developmental factors in adolescents encourage drug seeking behavior, and as a result, addiction.
203:
makes one individual more likely to develop an addiction than another individual. Additionally, many in the science community agree that addiction is not simply just a result of
52:– psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain
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1016:
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use, it has been shown to be physiologically altered. This compromised neural state plays a large role in perpetuating addiction and in making recovery more difficult.
279:
contribute to vulnerability because they can put the brain in a compromised state. External stressors (such as financial concerns and family problems) can, after
966:
Thanos, Panayotis K.; Gopez, Vanessa; Delis, Foteini; Michaelides, Michael; Grandy, David K.; Wang, Gene-Jack; Kunos, George; Volkow, Nora D. (1 January 2011).
173:
219:
Contemporary research in neurobiology (a branch of science that deals with the anatomy, physiology, and pathology of nervous system) of addiction points to
774:
Kreek, Mary Jeanne; Nielsen, David A.; LaForge, K. Steven (1 January 2004). "Genes
Associated With Addiction: Alcoholism, Opiate, and Cocaine Addiction".
1499:
Fergusson, D. M.; Boden, J. M.; Horwood, L. J. (2008). "The developmental antecedents of illicit drug use: Evidence from a 25-year longitudinal study".
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meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
376:
of their offspring (e.g., behavioral responses to environmental stimuli). In addiction, epigenetic mechanisms play a central role in the
1577:
Bates, M. E.; Labouvie, E. W. (1997). "Adolescent Risk
Factors and the Prediction of Persistent Alcohol and Drug Use into Adulthood".
968:"Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption"
107:– dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
521:
304:
addiction is the result of the shift from goal-directed actions to habits and ultimately, to compulsive drug-seeking and taking.
166:
401:
63:– an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
820:
Hyman, SE; Malenka, RC; Nestler, EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory".
392:
The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include
512:
Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and
Addictive Disorders". In Sydor A, Brown RY (eds.).
1776:
1325:"Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex"
726:
R. Maldonado, P. CalvĂ©, A. GarcĂa-Blanco, L. Domingo-Rodriguez, E. Senabre, E. MartĂn-GarcĂa. Vulnerability to addiction,
244:
159:
141:– a condition in which the use of substances leads to clinically and functionally significant impairment or distress
204:
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According to a review of experimental animal models that examined the transgenerational epigenetic inheritance of
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1712:"Transgenerational Inheritance of Paternal Neurobehavioral Phenotypes: Stress, Addiction, Ageing and Metabolism"
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372:, a phenomenon in which environmental influences on the genes of a parent can affect the associated traits and
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103:
137:
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in the brain and in the normal regulation of dopamine. Individuals with this genetic deficiency in the D
125:– stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
207:
neural receptors but also a corollary of long-term associated memories (or cues) of substance use and
1710:
Yuan TF, Li A, Sun X, Ouyang H, Campos C, Rocha NB, Arias-CarriĂłn O, Machado S, Hou G, So KF (2015).
1229:
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of cocaine-addicted male rats. These epigenetic alterations in the rat mPFC result in increased BDNF
445:
434:
397:
373:
224:
59:
1617:"Adolescents are more vulnerable to cocaine addiction: behavioral and electrophysiological evidence"
1280:(2005). "Neural systems of reinforcement for drug addiction: from actions to habits to compulsion".
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in which the addicted individual is able to maintain stability but at a pathological set point.
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This suggests that both of these genetic factors work together in the regulation of alcohol and
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149:– the diminishing effect of a drug resulting from repeated administration at a given dose
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role in addiction vulnerability when in combination with environmental factors. Chronic
75:– the escalating effect of a drug resulting from repeated administration at a given dose
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is a period of increased vulnerability to drug-seeking behavior and onset addiction.
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effects. The brain can physically “rewire” itself to accommodate for the increase in
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receptor, has been studied at length in association to substance addiction. The D
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280:
241:
408:. With respect to addiction, more research is needed to determine the specific
211:. Vulnerability to addiction has both physiological and biological components.
116:– stimuli that increase the probability of repeating behaviors paired with them
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Wong, WC; Ford, KA; Pagels, NE; McCutcheon, JE; Marinelli, M (13 March 2013).
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133:– an amplified response to a stimulus resulting from repeated exposure to it
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Range of genetic and environmental risk factors for developing an addiction
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676:"Mechanisms of transgenerational inheritance of addictive-like behaviors"
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over their genetically normal peers, but also compensated levels of the
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1378:
Philosophical
Transactions of the Royal Society B: Biological Sciences
1374:"The incentive sensitization theory of addiction: Some current issues"
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of the disease; it has been noted that some of the alterations to the
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593:"Neurobiologic Advances from the Brain Disease Model of Addiction"
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516:(2nd ed.). New York: McGraw-Hill Medical. pp. 364–375.
461:
1105:
Volkow, N.; Li, T. K. (2005). "The neuroscience of addiction".
40:
disorder characterized by persistent use of drugs (including
1218:"Chronic Stress, Drug Use, and Vulnerability to Addiction"
1153:"Chronic Stress, Drug Use, and Vulnerability to Addiction"
1421:
Koob, G. F. (2003). "Alcoholism: Allostasis and Beyond".
83:– symptoms that occur upon cessation of repeated drug use
44:) despite substantial harm and adverse consequences
23:
875:"The genetics of addictions: uncovering the genes"
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1144:
922:"Genetic susceptibility to substance dependence"
591:Volkow ND, Koob GF, McLellan AT (January 2016).
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325:culminates in the development of this disorder.
286:Chronic stress or trauma has been shown to have
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308:compulsive motivation and desire for the drug.
91:– dependence that involves persistent physical–
1579:Alcoholism: Clinical and Experimental Research
1536:The American Journal of Drug and Alcohol Abuse
1423:Alcoholism: Clinical and Experimental Research
972:Alcoholism: Clinical and Experimental Research
266:lead to increased vulnerability to addiction.
167:
8:
730:, Volume 186, 2021, 108466, ISSN 0028-3908,
1222:Annals of the New York Academy of Sciences
1157:Annals of the New York Academy of Sciences
754:Centers for Disease Control and Prevention
483:within the mPFC, which in turn blunts the
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1372:Robinson, T. E.; Berridge, K. C. (2008).
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189:is an individual's risk of developing an
1666:"Adolescent brain development and drugs"
548:"Cellular basis of memory for addiction"
437:that occur in addiction, alterations in
370:transgenerational epigenetic inheritance
361:Transgenerational epigenetic inheritance
355:Transgenerational epigenetic inheritance
1664:Winters, Ken C.; Arria, Amelia (2011).
1610:
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95:withdrawal symptoms (e.g., fatigue and
834:10.1146/annurev.neuro.29.051605.113009
467:– have been shown to occur within the
318:Experience-dependent neural plasticity
283:, affect the physiology of the brain.
20:
7:
674:Vassoler FM, Sadri-Vakili G (2014).
1591:10.1111/j.1530-0277.1997.tb03863.x
1435:10.1097/01.ALC.0000057122.36127.C2
1015:Nestler, Eric J. (November 2000).
692:10.1016/j.neuroscience.2013.07.064
552:Dialogues in Clinical Neuroscience
441:– specifically, di-acetylation of
14:
635:of severe substance-use disorder.
24:Addiction and dependence glossary
1513:10.1016/j.drugalcdep.2008.03.003
1216:Sinha, Rajita (1 October 2008).
984:10.1111/j.1530-0277.2010.01318.x
736:10.1016/j.neuropharm.2021.108466
1151:Sinha, Rajita (17 April 2017).
873:Goldman, Orozsi; Ducci (2005).
597:New England Journal of Medicine
487:of cocaine and reduces cocaine
1633:10.1523/JNEUROSCI.1371-12.2013
1329:American Journal of Psychiatry
402:downregulation or upregulation
1:
822:Annual Review of Neuroscience
1341:10.1176/appi.ajp.159.10.1642
750:"What is Epigenetics? | CDC"
546:Nestler EJ (December 2013).
1621:The Journal of Neuroscience
1501:Drug and Alcohol Dependence
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358:
1731:10.1007/s12035-015-9526-2
1670:The Prevention Researcher
1548:10.1080/00952990600753867
1323:Goldstein, R. Z. (2002).
155:
28:
920:Hiroi, Agatsuma (2005).
469:medial prefrontal cortex
104:psychological dependence
1242:10.1196/annals.1441.030
1177:10.1196/annals.1441.030
776:NeuroMolecular Medicine
187:Addiction vulnerability
1390:10.1098/rstb.2008.0093
460:) in association with
138:substance use disorder
1017:"Genes and Addiction"
939:10.1038/sj.mp.4001622
609:10.1056/NEJMra1511480
398:histone modifications
374:behavioral phenotypes
270:Environmental factors
1777:Addiction psychiatry
485:rewarding properties
1458:Nature Neuroscience
1384:(1507): 3137–3146.
1282:Nature Neuroscience
1234:2008NYASA1141..105S
1169:2008NYASA1141..105S
1119:10.1038/nn1105-1429
1107:Nature Neuroscience
1064:Nature Neuroscience
788:10.1385/NMM:5:1:085
748:CDC (18 May 2022).
489:self-administration
439:histone acetylation
209:self-administration
88:physical dependence
862:. 20 January 2024.
350:Epigenetic factors
314:allostatic changes
198:Three-factor model
68:drug sensitization
1464:(12): 1217–1223.
1335:(10): 1642–1652.
1288:(11): 1481–1489.
1113:(11): 1429–1430.
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728:Neuropharmacology
299:Repeated exposure
281:repeated exposure
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73:reverse tolerance
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394:DNA methylation
387:natural rewards
378:pathophysiology
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343:dopamine system
341:The mesolimbic
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215:Genetic factors
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80:drug withdrawal
38:biopsychosocial
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1429:(2): 232–243.
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1294:10.1038/nn1579
1278:Robbins, T. W.
1274:Everitt, B. J.
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1228:(1): 105–130.
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1076:10.1038/nn1583
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1027:(3): 277–281.
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926:Mol Psychiatry
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885:(7): 521–532.
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856:"Neurobiology"
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782:(1): 085–108.
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54:reward systems
49:addictive drug
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1010:
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205:desensitized
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1163:: 105–130.
686:: 198–206.
336:adolescence
329:Adolescence
242:cannabinoid
112:reinforcing
828:: 565–98.
499:References
366:Epigenetic
359:See also:
60:dependence
1185:0077-8923
450:histone 3
410:heritable
406:microRNAs
382:epigenome
277:stressors
191:addiction
146:tolerance
121:rewarding
33:addiction
1771:Category
1757:25694221
1749:26572641
1692:22822298
1651:23486962
1556:16864471
1521:18423900
1486:28573169
1478:11694884
1443:12605072
1408:18640920
1359:12359667
1310:16941967
1302:16251991
1260:18991954
1203:18991954
1127:16251981
1092:12589277
1084:16251987
1049:15704258
1041:11062465
1002:20958329
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899:15995696
842:16776597
804:29883440
796:15001815
710:23920159
627:26816013
574:24459410
471:(mPFC),
458:H3K14ac2
446:residues
292:cortisol
233:dopamine
221:genetics
1683:3399589
1642:3630505
1599:9267549
1564:6845644
1399:2607325
1350:1201373
1251:2732004
1230:Bibcode
1194:2732004
1165:Bibcode
1135:7721465
993:3004984
907:3842270
701:3872494
618:6135257
565:3898681
454:H3K9ac2
452:(i.e.,
255:cocaine
229:subtype
123:stimuli
114:stimuli
93:somatic
42:alcohol
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473:testes
443:lysine
400:, and
1753:S2CID
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1560:S2CID
1482:S2CID
1306:S2CID
1131:S2CID
1088:S2CID
1045:S2CID
903:S2CID
800:S2CID
477:sperm
421:Notes
1745:PMID
1688:PMID
1647:PMID
1595:PMID
1552:PMID
1517:PMID
1474:PMID
1439:PMID
1404:PMID
1355:PMID
1298:PMID
1256:PMID
1226:1141
1199:PMID
1181:ISSN
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1123:PMID
1080:PMID
1037:PMID
998:PMID
944:PMID
895:PMID
838:PMID
792:PMID
761:2022
706:PMID
623:PMID
570:PMID
518:ISBN
462:BDNF
456:and
36:– a
1735:hdl
1727:doi
1678:PMC
1637:PMC
1629:doi
1587:doi
1544:doi
1509:doi
1466:doi
1431:doi
1394:PMC
1386:doi
1382:363
1345:PMC
1337:doi
1333:159
1290:doi
1246:PMC
1238:doi
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1173:doi
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988:PMC
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887:doi
830:doi
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732:doi
696:PMC
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