Dopamine in the nucleus accumbens during cocaine self-administration as studied by in vivo microdialysis.

The extracellular dopamine (DA) concentration in the nucleus accumbens was measured following intravenous cocaine administration. The DA concentration increased in a dose-dependent manner following a single intravenous infusion of cocaine. The concentration of DA was observed to increase and stabilize in a schedule-dependent manner when cocaine was repeatedly administered 15-, 5- and 2.5-minute intervals. When cocaine was administered in regular intervals to animals by an experimenter or when animals self-administered cocaine. DA concentrations stabilized substantially above the basal level. These data support research that suggests that reinforcing properties of cocaine are primarily mediated by DA release in the nucleus accumbens. The data and pharmacokinetic calculations indicate that the DA concentration increases for a short period following each infusion. It then falls to a level until the animal again self-administers the drug. Animals may regulate self-administration responding for cocaine in order to maintain DA levels above a certain level, yet titrate responding so that aversive effects are not produced.