Synaptic plasticity in the mesolimbic system: therapeutic implications for substance abuse

Abstract

In an ever-changing environment, animals must learn new behavioral strategies for the successful procurement of food, sex, and other needs. Synaptic plasticity within the mesolimbic system, a key reward circuit, affords an animal the ability to adapt and perform essential goal-directed behaviors. Ironically, drugs of abuse can also induce synaptic changes within the mesolimbic system, and such changes are hypothesized to promote deleterious drug-seeking behaviors in lieu of healthy, adaptive behaviors. In this review, we will discuss drug-induced neuroadaptations in excitatory transmission in the ventral tegmental area and the nucleus accumbens, two critical regions of the mesolimbic system, and the possible role of dopamine receptors in the development of these neuroadaptations. In particular, we will focus our discussion on recent studies showing changes in AMPA receptor function as a common molecular target of addictive drugs, and the possible behavioral consequences of such neuroadaptations.