The effects of the preferential dopamine D(3) receptor antagonist S33138 on ethanol binge drinking in C57BL/6J mice.

The mesolimbic dopamine (DA) pathway plays an integral role in the reinforcing properties of many drugs of abuse, including alcohol (ethanol/EtOH). It has been reported that selective and acute blockade of the DA D3 receptor by SB-277011A will attenuate EtOH preference, intake, and lick responses in EtOH preferring rats. However, alcohol consumption that leads to abuse is often marked by binge drinking-which is characterized as bringing ones blood EtOH levels to ≥80 mg/dL within 2 hours of the initial drink. It is unclear if brain mechanisms implicated in EtOH reward are equally implicated in EtOH binge consumption and abuse. Therefore, in this study, we examined the effect of the preferential D3 receptor antagonist S33138 on ethanol (6% v/v) and water consumption in male C57BL/6J mice using a restricted-access binge-drinking model. Ethanol drinking was not significantly altered by the intraperitoneal (i.p.) administration of 0.16 mg/kg of S33138. In contrast, the i.p. administration of 0.64 or 2.5 mg/kg i.p. of S33138 produced a significant decrease in ethanol consumption on days 1 and 7 and days 7-14 compared to vehicle treated animals. However, the mean water consumption was significantly decreased by (1) 0.16 and 0.64 mg/kg i.p. of S33138 on Day 1 and (2) 2.5 mg/kg i.p. of S33138 at Days 1, 7, and 7-14. Our studies indicate that a low dose of S33138 significantly decreases binge drinking, and that it does not significantly alter the consumption of water. In addition, S33138 alone is not appetitive.