Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Rationale: Studies support differential roles of dopamine receptor subfamilies in the rewarding and reinforcing properties of drugs of abuse, including ethanol. However, the roles these receptor subfamilies play in ethanol reward are not fully delineated. Objective: To examine the roles of dopamine receptor subfamilies in the acquisition of ethanol-induced conditioned place preference (CPP), we pretreated animals systemically with antagonist drugs selective for dopamine D1-like (SCH-23390) and D2-like (raclopride) receptors prior to ethanol conditioning trials. Methods: Effects of raclopride (0-1.2 mg/kg) and SCH-23390 (0-0.3 mg/kg) on the acquisition of ethanol-induced CPP were examined in DBA/2J mice (experiments 1 and 2). Based on significant effects of SCH-23390, we then determined if SCH-23390 (0.3 mg/kg) produced a place preference on its own (experiment 3). To evaluate whether SCH-23390 impaired learning, we used a conditioned place aversion (CPA) paradigm and pretreated animals with SCH-23390 (0-0.3 mg/kg) before conditioning sessions with LiCl (experiment 4). Results: Whereas raclopride (0-1.2 mg/kg) did not affect acquisition, SCH-23390 (0.1-0.3 mg/kg) impaired the development of ethanol-induced CPP. SCH-23390 (0.3 mg/kg) did not produce place preference when tested alone and SCH-23390 (0.1-0.3 mg/kg) did not perturb the acquisition of LiCl-induced CPA. Conclusions: Our results support a role for dopamine D1-like but not D2-like receptors in ethanol's unconditioned rewarding effect as indexed by CPP. Blockade of D1-like receptors did not affect aversive learning in this procedure.