Receptor subtype-specific dopaminergic agents and conditioned behavior

Abstract

Dopaminergic neurotransmission has been implicated in reward-related learning. With the advent of pharmacological agents that are relatively specific for D1 and D2 dopamine receptors, it has become possible to assess the role of these receptor subtypes in this form of learning. Antagonist studies have shown that either D1 or D2 receptor blockers produced extinction-like effects on operant responding for food, water or brain stimulation reward and in drug self-administration paradigms. They also blocked place preference learning based on amphetamine. Agonist studies showed that D2, but not D1 agonists were self-administered, produced place preferences and enhanced responding for conditioned reward. It may be that the dopaminergic signal at the D1 receptor is important for the establishment and maintenance of reward-related learning. From this point of view the effects of D1 antagonists can be understood. D2 antagonists may produce extinction-like effects because they lead to increased dopamine release and, therefore, indirectly mask the dopamine signal at the D1 receptor. D1 agonists may fail to produce reward effects because they, unlike D2 agonists, directly mask the dopaminergic signal at the D1 receptor.