Dopamine Receptor Subtypes in Reward and Relapse

Abstract

With the advent of subtype-selective ligands and dopamine receptor knockout mice, the last two decades have seen an explosion in research on the role of dopamine receptor subtypes in reward and relapse to drug-seeking behav- ior. This chapter represents a relatively comprehensive review of this literature, beginning with the ability of D1-like and D2-like receptor agonists to support self- administration behavior and produce conditioned preference, and followed by the modulation of natural reward, brain stimulation reward, and conditioned reward with subtype-selective ligands and dopamine receptor knockout mice. Subsequent sec- tions describe the modulation of drug and alcohol self-administration by dopamine receptor subtypes, and role of dopamine receptor subtypes in relapse to drug and alcohol seeking in animal models. Finally, down-regulation in dopamine receptors following chronic drug self-administration is discussed in reference to differential changes in dopamine receptor-mediated behavior, suggesting that better integration between biological and behavioral data is needed in future studies.