The neurocircuitry of addiction: an overview

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British Journal of Pharmacology (2008) 154, 261–274

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REVIEW

The neurocircuitry of addiction: an overview
MW Feltenstein and RE See
Department of Neurosciences, Medical Universiy of South Carolina, Charleston, SC, USA

Drug addiction presents as a chronic relapsing disorder characterized bypersistent drug-seeking and drug-taking behaviours. Given the significant detrimental effects of this disease both socially and economically, a considerable amount of research has been dedicated to understanding a number of issues in addiction, including behavioural and neuropharmacological factors that contribute to the development, loss of control and persistence of compulsive addictivebehaviours. In this review, we will give a broad overview of various theories of addiction, animal models of addiction and relapse, drugs of abuse, and the neurobiology of drug dependence and relapse. Although drugs of abuse possess diverse neuropharmacological profiles, activation of the mesocorticolimbic system, particularly the ventral tegmental area, nucleus accumbens, amygdala and prefrontal cortexvia dopaminergic and glutamatergic pathways, constitutes a common pathway by which various drugs of abuse mediate their acute reinforcing effects. However, long-term neuroadaptations in this circuitry likely underlie the transition to drug dependence and cycles of relapse. As further elucidated in more comprehensive reviews of various subtopics on addiction in later sections of this special issue,it is anticipated that continued basic neuroscience research will aid in the development of effective therapeutic interventions for the long-term treatment of drug-dependent individuals.

British Journal of Pharmacology (2008) 154, 261–274; doi:10.1038/bjp.2008.51; published online 3 March 2008
Keywords: abuse; addiction; animal models; dopamine; glutamate; mesocorticolimbic; neurobiology;relapse Abbreviations: AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; BLA, basolateral amygdala; BNST, bed

nucleus of the stria terminalis; CeA, central nucleus of the amygdala; CPP, conditioned place preference; CRF, corticotropin-releasing factor; DA, dopamine; dmPFC, dorsomedial prefrontal cortex; ICSS, intracranial self-stimulation; NAcc, nucleus accumbens; NE, norepinephrine;OFC, orbitofrontal cortex; PFC, prefrontal cortex; VTA, ventral tegmental area

Introduction
Drug addiction is a chronic relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviours, despite negative consequences. The American Psychiatric Association (1994) describes substance dependence as a set of symptoms mainly involving the inability to reduce or control druguse, with the recent National Survey on Drug Use and Health (Substance Abuse and Mental Health Services Administration (SAMHSA, 2007) estimating that 22.6 million Americans 12 years of age or older, or 9.2% of the population, can be considered to have a substance abuse or dependence disorder (including alcohol or illicit drugs). Although evidence shows periodic declines in some areas of abusepatterns, the overall prevalence of substance abuse disorders remains unacceptably high. Moreover, one of the most significant problems for the long-term treatment of drug dependence is the high incidence of relapse to drug-seeking and drug-taking behaviours following months or years of abstinence (Dackis and O’Brien, 2001; Wagner and Anthony, 2002). Given the detrimental social and economic effects ofdrug addiction, a significant amount of research has been dedicated to ascertaining the neuropharmacological mechanisms mediating the development and persistence of substance abuse disorders. In this section of this special journal issue, we will provide a broad overview of how animal models of addiction and relapse have advanced our understanding of the neurobiology underlying drug-taking and...
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