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Lancaster Road, Dallas, TX Abstract Neurophysiologic processes underlie the uncontrolled, compulsive behaviors defining the addicted state. 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.
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