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Chapter 1. Neurobiology of Addiction

George F. Koob, Ph.D.
DOI: 10.1176/appi.books.9781585623440.344000

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Drug addiction, also known as substance dependence, is a chronic, relapsing disorder characterized by 1) compulsion to seek and take the drug, 2) loss of control in limiting intake, and 3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented (defined here as dependence) (Koob and Le Moal 1997). Addiction and substance dependence, as currently defined in DSM-IV-TR (American Psychiatric Association 2000), will be used interchangeably throughout this chapter and refer to a final stage of a usage process that moves from drug use to addiction. Clinically, the occasional but limited use of a drug with the potential for abuse or dependence is distinct from escalated drug use and the emergence of a chronic drug-dependent state. An important goal of current neurobiological research is to understand the neuropharmacological and neuroadaptive mechanisms within specific neurocircuits that mediate the transition from occasional, controlled drug use to the loss of behavioral control over drug seeking and drug taking that defines chronic addiction.

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FIGURE 1–1. Diagram showing stages of impulse control disorder and compulsive disorder cycles related to the sources of reinforcement.In impulse control disorders, an increasing tension and arousal occurs before the impulsive act, with pleasure, gratification, or relief during the act. Following the act there may or may not be regret or guilt. In compulsive disorders, there are recurrent and persistent thoughts (obsessions) that cause marked anxiety and stress followed by repetitive behaviors (compulsions) that are aimed at preventing or reducing distress (American Psychiatric Association 1994). Positive reinforcement (pleasure/gratification) is more closely associated with impulse control disorders. Negative reinforcement (relief of anxiety or relief of stress) is more closely associated with compulsive disorders.Source. Reprinted from Koob GF: "Allostatic View of Motivation: Implications for Psychopathology," in Motivational Factors in the Etiology of Drug Abuse (Nebraska Symposium on Motivation, Volume 50). Lincoln, NE, University of Nebraska Press, 2004. Used with permission.

FIGURE 1–2. Diagram describing the addiction cycle—preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect—from a psychiatric perspective with the different criteria for substance dependence incorporated from DSM.

FIGURE 1–3. Sagittal section through a representative rodent brain illustrating the pathways and receptor systems implicated in the acute reinforcing actions of drugs of abuse.Cocaine and amphetamines activate the release of dopamine in the nucleus accumbens and amygdala via direct actions on dopamine terminals. Opioids activate opioid receptors in the ventral tegmental area, nucleus accumbens, and amygdala via direct actions on interneurons. Opioids facilitate the release of dopamine in the nucleus accumbens via an action either in the ventral tegmental area or the nucleus accumbens, but are also hypothesized to activate elements independent of the dopamine system. Alcohol activates -aminobutyric acidA (GABAA) receptors in the ventral tegmental area, nucleus accumbens, and amygdala via either direct actions at the GABAA receptor or through indirect release of GABA. Alcohol is hypothesized to facilitate the release of opioid peptides in the ventral tegmental area, nucleus accumbens, and central nucleus of the amygdala. Alcohol facilitates the release of dopamine in the nucleus accumbens via an action either in the ventral tegmental area or the nucleus accumbens. Nicotine activates nicotinic acetylcholine receptors in the ventral tegmental area, nucleus accumbens, and amygdala, either directly or indirectly, via actions on interneurons. Nicotine may also activate opioid peptide release in the nucleus accumbens or amygdala, independent of the dopamine system. Cannabinoids activate cannabinoid type 1 (CB1) receptors in the ventral tegmental area, nucleus accumbens, and amygdala via direct actions on interneurons. Cannabinoids facilitate the release of dopamine in the nucleus accumbens via an action either in the ventral tegmental area or the nucleus accumbens, but are also hypothesized to activate elements independent of the dopamine system. Endogenous cannabinoids may interact with postsynaptic elements in the nucleus accumbens involving dopamine and/or opioid peptide systems. The blue arrows represent the interactions within the extended amygdala system hypothesized to have a key role in psychostimulant reinforcement. AC = anterior commissure; AMG = amygdala; ARC = arcuate nucleus; BNST = bed nucleus of the stria terminalis; Cer = cerebellum; C-P = caudate-putamen; DMT = dorsomedial thalamus; FC = frontal cortex; Hippo = hippocampus; IF = inferior colliculus; LC = locus coeruleus; LH = lateral hypothalamus; N Acc = nucleus accumbens; OT = olfactory tract; PAG = periaqueductal gray; RPn = reticular pontine nucleus; SC = superior colliculus; SNr = substantia nigra pars reticulata; VP = ventral pallidum; VTA = ventral tegmental area.Source. Reprinted from Koob GF: "The Neurocircuitry of Addiction: Implications for Treatment." Clinical Neuroscience Research 5:89–101, 2005. Used with permission.

FIGURE 1–4. Key common neurocircuitry elements in drug-seeking behavior of addiction.Three major circuits that underlie addiction can be distilled from the literature. A drug reinforcement circuit (reward and stress) is composed of the extended amygdala, including the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the transition zone in the shell of the nucleus accumbens. Multiple modulator neurotransmitters are hypothesized, including dopamine and opioid peptides for reward; and corticotropin-releasing factor and norepinephrine for stress. The extended amygdala is hypothesized to mediate integration of rewarding stimuli or stimuli with positive incentive salience and aversive stimuli or stimuli with negative aversive salience. During acute intoxication, valence is weighted on processing rewarding stimuli, and, during the development of dependence, aversive stimuli come to dominate function. A drug- and cue-induced reinstatement (craving) neurocircuit is composed of the prefrontal (anterior cingulate, prelimbic, orbitofrontal) cortex and basolateral amygdala, with a primary role hypothesized for the basolateral amygdala in cue-induced craving and a primary role for the medial prefrontal cortex in drug-induced craving, based on animal studies. Human imaging studies have shown an important role for the orbitofrontal cortex in craving (see text). A drug-seeking circuit (compulsive) circuit is composed of the nucleus accumbens, ventral pallidum, thalamus, and orbitofrontal cortex. The nucleus accumbens has long been hypothesized to have a role in translating motivation to action and forms an interface between the reward functions of the extended amygdala and the motor functions of the ventral striatal–ventral pallidal–thalamic-cortical loops. The striatal-pallidal-thalamic loops reciprocally move from prefrontal cortex to orbitofrontal cortex to motor cortex—ultimately leading to drug-seeking behavior. Note that, for the sake of simplicity, other structures are not included, such as the hippocampus (which presumably mediates context-specific learning, including that associated with drug actions). Also note that dopamine and norepinephrine both have widespread innervation of cortical regions and may modulate function relevant to drug addiction in those structures. CRF = corticotropin-releasing factor; DA = dopamine; -END = -endorphin; ENK = emkephalin; NE = norepinephrine; VTA = ventral tegmental area.Source. Reprinted from Koob GF, Le Moal M: Neurobiology of Addiction. London, Academic Press, 2005. Used with permission.
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TABLE 1–1. Animal models for the motivational component of dependence
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TABLE 1–2. Neurobiological substrates for the acute reinforcing effects of drugs of abuse
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TABLE 1–3. Neurotransmitters implicated in the motivational effects of withdrawal from drugs of abuse
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TABLE 1–4. Drug craving
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The brain reward system implicated in the development of addiction comprises key elements of the basal forebrain such as the ventral striatum, the extended amygdala, and its connections.

Neuropharmacological studies in animal models of addiction have provided evidence to indicate that there are decreases of specific neurochemical mechanisms in specific brain reward neurochemical systems in the ventral striatum and amygdala (dopamine, opioid peptides, -aminobutyric acid, and endocannabinoids; light side of addiction).

Recruitment of brain stress systems (corticotropin-releasing factor and norepinephrine; dark side of addiction) and dysregulation of brain anti-stress systems (neuropeptide Y) provide the negative motivational state associated with drug abstinence.

Changes in the reward and stress systems are hypothesized to maintain hedonic stability in an allostatic state (altered reward set point), as opposed to a homeostatic state and, as such, convey the vulnerability for the development of dependence and relapse in addiction.

Similar neurochemical systems have been implicated in animal models of relapse, with dopamine and opioid peptide systems (and glutamate) being implicated in drug- and cue-induced relapse, possibly more in prefrontal cortical and basolateral amygdala projections to the ventral striatum and extended amygdala than in the reward system itself. The brain stress systems in the extended amygdala are directly implicated in stress-induced relapse.

Genetic studies to date in animals using knockouts of specific genes suggest roles for the genes encoding the neurochemical elements involved in the brain reward (dopamine, opioid peptide) and stress (neuropeptide Y) systems in the vulnerability to addiction.

References

Alheid GF, De Olmos JS, Beltramino CA: Amygdala and extended amygdala, in The Rat Nervous System. Edited by Paxinos G. San Diego, CA, Academic Press, 1995, pp 495–578
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Association, 1994
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000
 
Bonson KR, Grant SJ, Contoreggi CS, et al: Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376–386, 2002
[PubMed]
 
Breiter HC, Aharon I, Kahneman D, et al: Functional imaging of neural responses to expectancy and experience of monetary gains and losses. Neuron 30:619–639, 2001
[PubMed]
 
Caine SB, Negus SS, Mello NK, et al: Role of dopamine D2-like receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonists. J Neurosci 22:2977–2988, 2002
[PubMed]
 
Caine SB, Thomsen M, Gabriel KI, et al: Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice. J Neurosci 27:13140–13150, 2007
[PubMed]
 
Carr LG, Foroud T, Bice P, et al: A quantitative trait locus for alcohol consumption in selectively bred rat lines. Alcohol Clin Exp Res 22:884–887, 1998
[PubMed]
 
Childress AR, Mozley PD, McElgin W, et al: Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156:11–18, 1999
[PubMed]
 
Collins AC, Bhat RV, Pauly JR, et al: Modulation of nicotine receptors by chronic exposure to nicotinic agonists and antagonists, in The Biology of Nicotine Dependence (Ciba Foundation Symposium, Vol 152). Edited by Bock G, Marsh J. New York, Wiley, 1990, pp 87–105
 
Contet C, Kieffer BL, Befort K: Mu opioid receptor: a gateway to drug addiction. Curr Opin Neurobiol 14:370–378, 2004
[PubMed]
 
Dani JA, Heinemann S: Molecular and cellular aspects of nicotine abuse. Neuron 16:905–908, 1996
[PubMed]
 
Davidson M, Shanley B, Wilce P: Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study. Brain Res 674:91–96, 1995
[PubMed]
 
Delfs JM, Zhu Y, Druhan JP, et al: Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403:430–434, 2000
[PubMed]
 
De Witte P, Littleton J, Parot P, et al: Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action. CNS Drugs 19:517–537, 2005
 
Epping-Jordan MP, Watkins SS, Koob GF, et al: Dramatic decreases in brain reward function during nicotine withdrawal. Nature 393:76–79, 1998
[PubMed]
 
Everitt BJ, Wolf ME: Psychomotor stimulant addiction: a neural systems perspective. J Neurosci 22:3312–3320, 2002; erratum in J Neurosci 22:1a, 2002
 
Gardner EL, Vorel SR: Cannabinoid transmission and reward-related events. Neurobiol Dis 5:502–533, 1998
[PubMed]
 
Gaveriaux-Ruff C, Kieffer BL: Opioid receptor genes inactivated in mice: the highlights. Neuropeptides 36:62–71, 2002
[PubMed]
 
Gorelick DA, Kim YK, Bencherif B, et al: Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving. Biol Psychiatry 57:1573–1582, 2005
[PubMed]
 
Heimer L, Alheid G: Piecing together the puzzle of basal forebrain anatomy, in The Basal Forebrain: Anatomy to Function (Advances in Experimental Medicine and Biology, Vol 295). Edited by Napier TC, Kalivas PW, Hanin I. New York, Plenum, 1991, pp 1–42
 
Heinz A, Siessmeier T, Wrase J, et al: Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 161:1783–1789, 2004; erratum in Am J Psychiatry 161:2344, 2004
 
Heinz A, Reimold M, Wrase J, et al: Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 62:57–64, 2005; erratum in Arch Gen Psychiatry 62:983, 2005
 
Justinova Z, Tanda G, Munzar P, et al: The opioid antagonist naltrexone reduces the reinforcing effects of delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. Psychopharmacology (Berl) 173:186–194, 2004
[PubMed]
 
Justinova Z, Solinas M, Tanda G, et al: The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys. J Neurosci 25:5645–5650, 2005
[PubMed]
 
Koob GF: Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 27:232–243, 2003
[PubMed]
 
Koob GF: Allostatic view of motivation: implications for psychopathology, in Motivational Factors in the Etiology of Drug Abuse (Nebraska Symposium on Motivation, Vol 50). Lincoln, University of Nebraska Press, 2004, pp 1–18
 
Koob GF: The neurocircuitry of addiction: implications for treatment. Clin Neurosci Res 5:89–101, 2005
 
Koob GF, Bloom FE: Cellular and molecular mechanisms of drug dependence. Science 242:715–723, 1988
[PubMed]
 
Koob GF, Le Moal M: Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58, 1997
[PubMed]
 
Koob GF, Le Moal M: Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129, 2001
[PubMed]
 
Koob GF, Le Moal M: Plasticity of reward neurocircuitry and the 'dark side' of drug addiction. Nat Neurosci 8:1442–1444, 2005
[PubMed]
 
Koob GF, Le Moal M: Neurobiology of Addiction. London, Academic Press, 2006
 
Koob GF, Heinrichs SC, Menzaghi F, et al: Corticotropin releasing factor, stress and behavior. Seminars in the Neurosciences 6:221–229, 1994
 
Koob GF, Sanna PP, Bloom FE: Neuroscience of addiction. Neuron 21:467–476, 1998
[PubMed]
 
Koob GF, Bartfai T, Roberts AJ: The use of molecular genetic approaches in the neuropharmacology of corticotropin-releasing factor. Int J Comp Psychol 14:90–110, 2001
 
Lee JH, Lim Y, Wiederhold BK, et al: A functional magnetic resonance imaging (FMRI) study of cue-induced smoking craving in virtual environments. Appl Psychophysiol Biofeedback 30:195–204, 2005
[PubMed]
 
Markou A, Koob GF: Post-cocaine anhedonia: an animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26, 1991
[PubMed]
 
Martin WR: Opioid antagonists. Pharmacol Rev 19:463–521, 1967
[PubMed]
 
McBride WJ, Murphy JM, Lumeng L, et al: Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats. Alcohol 7:199–205, 1990
[PubMed]
 
McFarland K, Kalivas PW: The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 21:8655–8663, 2001
[PubMed]
 
Merlo-Pich E, Lorang M, Yeganeh M, et al: Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci 15:5439–5447, 1995
[PubMed]
 
Morrisett RA: Potentiation of N-methyl-d-aspartate receptor-dependent afterdischarges in rat dentate gyrus following in vitro ethanol withdrawal. Neurosci Lett 167:175–178, 1994
[PubMed]
 
Murphy JM, Stewart RB, Bell RL, et al: Phenotypic and genotypic characterization of the Indiana University rat lines selectively bred for high and low alcohol preference. Behav Genet 32:363–388, 2002
[PubMed]
 
Nestler EJ: Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci 25:210–218, 2004
[PubMed]
 
Olive MF, Koenig HN, Nannini MA, et al: Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake. Pharmacol Biochem Behav 72:213–220, 2002
[PubMed]
 
Pandey SC: The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction. Pharmacol Ther 104:47–58, 2004
[PubMed]
 
Parsons LH, Justice JB Jr: Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Brain Res 606:195–199, 1993
[PubMed]
 
Parsons LH, Weiss F, Koob GF: Serotonin-1B receptor stimulation enhances cocaine reinforcement. J Neurosci 18:10078–10089, 1998
[PubMed]
 
Paterson NE, Myers C, Markou A: Effects of repeated withdrawal from continuous amphetamine administration on brain reward function in rats. Psychopharmacology (Berl) 152:440–446, 2000
[PubMed]
 
Rasmussen DD, Boldt BM, Bryant CA, et al: Chronic daily ethanol and withdrawal, 1: long-term changes in the hypothalamo-pituitary-adrenal axis. Alcohol Clin Exp Res 24:1836–1849, 2000
[PubMed]
 
Risinger RC, Salmeron BJ, Ross TJ, et al: Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. Neuroimage 26:1097–1108, 2005
[PubMed]
 
Rivier C, Bruhn T, Vale W: Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF). J Pharmacol Exp Ther 229:127–131, 1984
[PubMed]
 
Roberts AJ, Cole M, Koob GF: Intra-amygdala muscimol decreases operant ethanol self-administration in dependent rats. Alcohol Clin Exp Res 20:1289–1298, 1996
[PubMed]
 
Roy A, Pandey SC: The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure. Alcohol Clin Exp Res 26:796–803, 2002
[PubMed]
 
Schulteis G, Markou A, Gold LH, et al: Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. J Pharmacol Exp Ther 271:1391–1398, 1994
[PubMed]
 
Schulteis G, Markou A, Cole M, et al: Decreased brain reward produced by ethanol withdrawal. Proc Natl Acad Sci U S A 92:5880–5884, 1995
[PubMed]
 
Shaham Y, Shalev U, Lu L, et al: The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20, 2003
[PubMed]
 
Shalev U, Grimm JW, Shaham Y: Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42, 2002
[PubMed]
 
Shippenberg TS, Koob GF: Recent advances in animal models of drug addiction and alcoholism, in Neuropsychopharmacology: The Fifth Generation of Progress. Edited by Davis KL, Charney D, Coyle JT, et al. Philadelphia, PA, Lippincott Williams & Wilkins, 2002, pp 1381–1397
 
Stinus L, Le Moal M, Koob GF: Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37:767–773, 1990
[PubMed]
 
Tiffany ST, Carter BL, Singleton EG: Challenges in the manipulation, assessment and interpretation of craving relevant variables. Addiction 95 (suppl 2):S177–S187, 2000
 
Tomkins DM, O'Neill MF: Effect of 5-HT(1B) receptor ligands on self-administration of ethanol in an operant procedure in rats. Pharmacol Biochem Behav 66:129–136, 2000
[PubMed]
 
United Nations International Drug Control Programme and World Health Organization: Informal Expert Group Meeting on the Craving Mechanism, Vienna, January 28–30, 1992 (report no. V92-54439T). Geneva, World Health Organization, 1992
 
Valdez GR, Roberts AJ, Chan K, et al: Increased ethanol self-administration and anxiety-like behavior during acute withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol Clin Exp Res 26:1494–1501, 2002
[PubMed]
 
Volkow ND, Wang GJ, Telang F, et al: Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26:6583–6588, 2006
[PubMed]
 
Vorel SR, Liu X, Hayes RJ, et al: Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292:1175–1178, 2001
[PubMed]
 
Weiss F, Markou A, Lorang MT, et al: Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res 593:314–318, 1992
[PubMed]
 
Weiss F, Parsons LH, Schulteis G, et al: Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci 16:3474–3485, 1996
[PubMed]
 
Weiss F, Ciccocioppo R, Parsons LH, et al: Compulsive drug-seeking behavior and relapse: neuroadaptation, stress, and conditioning factors, in The Biological Basis of Cocaine Addiction (Annals of the New York Academy of Sciences Vol 937). Edited by Quinones-Jenab. New York, New York Academy of Sciences, 2001, pp 1–26
 
Wong DF, Kuwabara H, Schretlen DJ, et al: Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving [erratum in: Neuropsychopharmacology 2006; 32:256]. Neuropsychopharmacology 31:2716–2727, 2006
[PubMed]
 
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Which of the following animal models is associated with the preoccupation/anticipation stage of addiction to explain the behavioral aspects of drug dependence in patients?
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Drug dependence has been modeled as both impulse control disorder and as compulsive disorder, two models that feature different drug-related behaviors. Which of the following behaviors is associated with impulse control disorder as opposed to compulsive disorder?
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Several neurobiological substrates have been identified to explain the acute reinforcing effects of abused drugs. These models include both specific neurotransmitters and anatomical foci. Which drug of abuse is associated with the neurotransmitters dopamine, -aminobutyric acid (GABA), and opioid peptides and the anatomic loci of the nucleus accumbens, ventral tegmental area, and amygdala?
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