A Role for Dopamine D1 Receptors in Ethanol Reward

M.M. Pina, C.L. Cunningham 

Dopaminergic transmission has been implicated in ethanol reward and involvement of dopamine D1 and D2 receptors has been examined using various pharmacological and genetic manipulations. However, studies assessing the consequences of systemic blockade of these receptors on the development of a place preference induced by ethanol remain largely absent from the literature. In the present experiments, we used systemic administration of selective dopamine receptor antagonists to examine the roles of D1 and D2 receptors in the acquisition of ethanol-induced conditioned place preference (CPP) in adult male DBA/2J mice. In experiments 1 and 2, antagonists selective for D2 (raclopride, 0-1.2 mg/kg) and D1 (SCH-23390, 0-0.3 mg/kg) receptors were administered before conditioning sessions, where ethanol (2 g/kg) was paired with a distinctive tactile floor cue. While antagonism of D2 receptors produced no effect, D1 receptor blockade impaired ethanol-CPP acquisition.  In experiment 3, we determined these impairments were not due to aversive properties of SCH-23390 (0.3 mg/kg), by demonstrating the inability of this drug to produce a conditioned place aversion (CPA). Experiment 4 examined the effect of SCH-23390 on the development of a CPA produced by post-trial ethanol (2 g/kg) injection. Ethanol-CPA was not impaired by SCH-23390, suggesting that reductions in ethanol-CPP acquisition were likely not due to general learning or memory impairments produced by the drug. These findings suggest that D1 receptor function is specific to the rewarding and not aversive motivational effects of ethanol. Supported by NIH-NIAAA grant AA07702.