Involvement of the sigma1 receptor in the motivational effects of ethanol in mice

Abstract In the present study, we examined the involvement of the sigma 1 (σ 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 σ 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 σ 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 σ 1 receptor ligand was devoid of behavioral effect by itself. These observations show that activation of the σ 1 receptor is a necessary component of ethanol-induced motivational effects and suggest a new pharmacological target for alleviating ethanol addiction.