Psychomotor stimulant addiction: a neural systems perspective.

The reinforcing (rewarding) effects of psychomotor stimulants (cocaine and amphetamine) depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens (Wise, 1981; for review, see Koob, 1992), perhaps especially the shell subregion (Bassareo and Di Chiara, 1997). Prominent theories of addiction are based on adaptations associated with both sensitization to and withdrawal from repeated exposure to psychomotor stimulants (Robinson and Berridge, 1993; Koob and Le Moal, 2001). Great progress has been achieved toward revealing the nature of cellular and molecular adaptations in animal models of addiction (Hyman and Malenka, 2001; Koob and Le Moal, 2001; Nestler, 2001), many of which are similar, if not identical, to those implicated in models of learning and memory (Hyman and Malenka, 2001; Nestler, 2001). One challenge in addiction research is to understand how molecular and cellular adaptations are related to altered functioning of neural systems that underlie compulsive drug-seeking behavior. This review highlights associative influences on psychomotor stimulant addiction, building on the view that plasticity in neural systems converging on the nucleus accumbens (Nac) and dorsal striatum (DS) is usurped by chronic drug selfadministration, leading to the aberrant engagement of pavlovian and instrumental learning processes. At a systems level, one product of the gradual strengthening or “consolidation ” of behavior arising from the reinforcing action of drugs may be the eventual progression of addiction to a form of habit-based learning, in which voluntary control over drug use is lost and the propensity to relapse is high and readily precipitated by exposure to drug-associated stimuli (O’Brien and McLellan, 1996; Robbins