Journal
HARVARD REVIEW OF PSYCHIATRY
Volume 12, Issue 6, Pages 305-320Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1080/10673220490910844
Keywords
amygdala; cocaine; cues; dopamine; impulsive behavior; nucleus accumbens; substance-related disorders; ventral tegmental area
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Funding
- NIAAA NIH HHS [AA1570, R01 AA011570-05] Funding Source: Medline
- NIDA NIH HHS [DA11434, R01 DA011434-02, R01 DA011434] Funding Source: Medline
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Neurophysiologic processes underlie the uncontrolled, compulsive behaviors defining the addicted state. These hard-wired changes in the brain are considered critical for the transition from casual to addictive drug use. This review of preclinical and clinical (primarily neuroimaging) studies will describe how the delineation between pleasure, reward, and addiction has evolved as our understanding of the biologic mechanisms underlying these processes has progressed. Although the mesolimbic dopaminergic efflux associated with drug reward was previously considered the biologic equivalent of pleasure, dopaminergic activation occurs in the presence of unexpected and novel stimuli (either pleasurable or aversive) and appears to determine the motivational state of wanting or expectation. The persistent release of dopamine during chronic drug use progressively recruits limbic brain regions and the prefrontal cortex, embedding drug cues into the amygdala (through glutaminergic mechanisms) and involving the amygdala, anterior cingulate, orbitofrontal cortex, and dorsolateral prefrontal cortex in the obsessive craving for drugs. The abstinent, addicted brain is subsequently primed to return to drug use when triggered by a single use of drug, contextual drug cues, craving, or stress, with each process defined by a relatively distinct brain region or neural pathway. The compulsive drive toward drug use is complemented by deficits in impulse control and decision making, which are also mediated by the orbitofrontal cortex and anterior cingulate. Within this framework, future targets for pharmacologic treatment are suggested.
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