Influence of sigma-1 receptor modulators on ethanol-induced conditioned place preference in the extinction-reinstatement model

Sigma-1 receptor agonists are reported to augment and antagonists block the rewarding effects of drugs of abuse. However, their effect on reinstatement of ethanol-induced conditioned place preference (CPP) has not yet been explored. Therefore, we investigated the ability of 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate (PRE-084), a sigma-1 receptor agonist, and N-2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD-1047), a sigma-1 receptor antagonist, on the acquisition, expression, and reinstatement of ethanol-induced CPP using adult male Swiss mice. BD-1047 (0.1-10 μg/mouse, intracerebroventricularly) dose-dependently blocked the development, expression, and reinstatement of ethanol-induced CPP, and PRE-084 (0.01-10 μg/mouse, intracerebroventricularly) dose-dependently reinstated the extinguished response. These effects of PRE-084 and BD-1047 alone or in combination with ethanol did not influence the motor activity. Therefore, it is concluded that sigma-1 receptor ligands can modulate the acquisition, expression, and reinstatement of conditioned reinforcing effects of ethanol with no reinforcing or aversive influence of their own. The results add to the growing literature on sigma-1 receptor modulation in the pharmacotherapy of ethanol addiction.