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

Pharmacol Biochem Behav. 2003 Mar;74(4):869-76. doi: 10.1016/s0091-3057(03)00002-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Male
  • Mice
  • Motivation*
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / physiology*
  • Sigma-1 Receptor

Substances

  • Receptors, sigma
  • Ethanol