The role of the striatum in addiction

Addiction is a notorious treatment-resistant psychiatric disorder characterized by the impairment of self-monitoring, loss of interest in other targets of pleasure, and uncorrectable impulsive/compulsive drug-seeking behaviors. The striatum, particularly the ventral striatum (= the nucleus accumbens) is deeply involved in the acquisition and expression of addiction. Although only few pharmacotherapeutic approaches against addiction are available, the currently used animal models of addiction are sophisticated enough to mimic most of the representative phenotypes observed in human addicts. In addition, recent advances in neuroimaging techniques, such as positron emission tomography or functional magnetic resonance imaging, as well as computational neuroscience approaches have promoted our understanding of addiction, particularly at the circuitry level. In this review, I introduce some pivotal topics regarding addiction for discussion. First, I outline the updated concept regarding how dopamine is involved in addiction by focusing on 2 seemingly uncompromising hypotheses, prediction-error theory and incentive salience theory. Second, after providing a brief introduction to unmanageable maladaptive behaviors in addiction that may be attributable to the impairments of the medial prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex, I emphasize the roles of glutamatergic inputs projecting from these frontal areas to the nucleus accumbens in cue-primed reinstatement of drug-seeking and impaired neuronal plasticity. Third, on the basis of the complementary or counterbalancing relationship between goal-directed behaviors and habits, I discuss the foresights and pitfalls of the current concept of "addiction as a pathological habit." Lastly, I conclude my discussion with an integrated (but a rough) circuitry model of addiction.