Involvement of the sigma 1 receptor in the motivational effects of ethanol in mice.

In the present study, we examined the involvement of the sigma(1) (sigma(1)) receptor in several behavioral manifestations of ethanol addiction. Administration of ethanol (0.5, 1, and 2 g/kg) in Swiss mice dose-dependently induced locomotor stimulation, conditioned place preference, and conditioned taste aversion, which are considered as behavioral index of drug-induced reward. Pretreatment with the selective sigma(1) receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047, 3-30 mg/kg) dose-dependently blocked ethanol (1 g/kg)-induced hyperlocomotion and taste aversion and ethanol (2 g/kg)-induced place preference. Pretreatment with the selective sigma(1) receptor agonist 2-(4-morpholino)ethyl 1-phenylcyclohexane-1-carboxylate (PRE-084, 1-10 mg/kg) before ethanol (0.5 g/kg) failed to affect the resulting locomotor stimulation, but dose-dependently enhanced the conditioned place preference. Each sigma(1) receptor ligand was devoid of behavioral effect by itself. These observations show that activation of the sigma(1) receptor is a necessary component of ethanol-induced motivational effects and suggest a new pharmacological target for alleviating ethanol addiction.