Dopaminergic mechanism of reward-related incentive learning: focus on the dopamine D(3) receptor.

Dopamine D(3) receptors (Drd3) have been implicated in the control of responding by drug-related conditioned incentive stimuli. We review recent studies of the effects of Drd3 antagonists or partial agonists on the control of self-administration of intravenous (IV) cocaine, IV morphine and oral ethanol on reward-rich and lean schedules, in reinstatement tests, on second-order schedules and on the acquisition and expression of conditioned place preference (CPP) and conditioned motor activity. For comparison, related studies where conditioned stimuli are based on nutritional reward also are considered. When self-administration depends more heavily on conditioned cues for its maintenance, for example on second-order schedules or lean ratio schedules, Drd3 antagonists or partial agonists reduce responding. Although data are limited, similar effects may be seen for responding for cues based on drugs or nutritional rewards. Drd3 agents also block the ability of conditioned cues to reinstate responding for cocaine or food. Published results suggest that Drd3 plays a more important role in the expression than in the acquisition of a CPP or conditioned motor activity. The mechanism mediating the role of Drd3 in the control of responding by conditioned incentive stimuli remains unknown but it has been found that Drd3 receptors increase in number in the nucleus accumbens during conditioning. Perhaps Drd3 participates in the molecular mechanisms underlying the role of dopamine and of dopamine receptor subtypes in reward-related incentive learning.