title: Involvement of the sigma 1 receptor in the motivational effects of ethanol in mice.
abstract: 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.
authors.affiliation: Behavioral Neuropharmacology Group, Institut de Biologie, INSERM U. 336, 4, bvd Henri IV, 34060 Montpellier, France. maurice@univ-montp2.fr
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Magali
authors.initials: M
authors.lastname: Casalino
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix
authors.forename: Pascal
authors.initials: P
authors.lastname: Romieu
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology*; D000097605:Sigma-1 Receptor
chemical_list: D000431:Ethanol; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor