The selective D3 receptor antagonist SB-277011A attenuates morphine-triggered reactivation of expression of cocaine-induced conditioned place preference.

We examined the effect of acute administration of the selective D3 receptor antagonist SB-277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB-277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB-277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB-277011A decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior, that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction.

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.