Functional significance of mesolimbic dopamine

Abstract

Although a large body of neuropharmacological evidence suggests that the mesolimbic dopamine system (ML DA) is critical for goal-directed behaviors, exactly which aspects of behavior are mediated or modulated by this system remains a matter of conjecture. By measuring changes in DA cell firing patterns and extracellular DA concentrations in target areas of ML DA cells during the development and performance of goal-directed behavior, it is possible to directly examine the relationship between ML DA transmission and various stages and components of behavior. This permits tests of hypotheses concerned with the functional significance of ML DA. This review will discuss recent electrophusiological, microdialysis and electrochemical data on behavior-associated changes in firing activity of ML DA cells and fluctuations in DA concentrations in target areas of these cells. Although application of an electrochemical technique to study behavior-associated changes in DA transmission is an area of hot debates, a close correlation between DA-dependent electrochemical signal changes and separate behavioral components, with a generally similar pattern of rapid signal fluctuations found in trained animals during operant lever-pressing behavior maintained by palatable food, cocaine or heroin, suggests that extrasynaptic DA may have some important functions in regulating behavior. This review will discuss possible mechanisms underlying phasic and tonic changes in ML DA transmission accompanying development and performance of positively-reinforced behavior, the contribution of learning, behavioral and pharmacological variables in the mediation of these changes, and their relevance for the organization and regulation of goal-directed behavior.