Neurocircuitry of Addiction

Addiction can be defined as drug-induced changes in the central nervous system (CNS) that produce maladaptive alterations in spontaneous behavior and in the behavioral response to readministration of that drug. Maladaptive behaviors include those identified as criteria for addiction in the DSM-IV. In general what most psychiatric metrics describe as addiction associated behaviors is the emergence of behaviors to obtain drug reward at the expense of engaging in behaviors to seek natural rewards, ranging from biological rewards such as sex to cultural rewards such as stable personal relationships. The substitution of drug reward for natural reward suggests that the neuropathology of addiction may reside in the same neural systems that mediate the detection and acquisition of natural rewards. This postulate forms a primary premise in the search for the neurobiological basis of addiction, and has revealed a circuit consisting of interconnections among limbic cortex, basal ganglia, and brainstem nuclei that is pathologically modified by repeated drug administration. The drug-induced changes in the structure and function of this circuit are progressive, and to some extent parallel the development of the behavioral characteristics of addiction. Over the last decade neurobiologists have come to describe the behavioral transition to addiction as a druginduced neuroplastic process (1–3). In parallel with the development and expression of addictive behaviors, the neurobiology of these two components of the transition to addiction can be described as: (a) the sequence of molecular events that establish the neuroplastic changes leading to addiction, and (b) the neuroplastic changes themselves. Accordingly, a number of molecular neuroplastic alterations have been identified in the brain after repeated drug administration, and some of these appear to be important in the development and/or expression of addictive behaviors. However, the process of identifying drug-induced changes is accelerating and producing a deluge of information that is proving increasingly difficult to integrate into a coherent sequence of neuroplastic changes that mediate addiction. In