1. ¹Department of Neurobiology, Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX, USA
2. ²The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA, USA
3. ³Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY, USA

Correspondence: Dr YA Blednov, Department of Neurobiology, Waggoner Center for Alcohol and Addiction Research, university of Texas, 1 University Station A4800, Austin, TX 78712-0159, USA. Tel: +1 512 232 2520; Fax: +1 512 232 2525; E-mail: yablednov@mail.utexas.edu

Received 4 May 2006; Revised 11 October 2006; Accepted 13 October 2006; Published online 13 December 2006.

Abstract

Endocannabinoid signaling plays the important role in regulation of ethanol intake. Fatty acid amide hydrolase (FAAH) is a key membrane protein for metabolism of endocannabinoids, including anandamide, and blockade of FAAH increases the level of anandamide in the brain. To determine if FAAH regulates ethanol consumption, we studied mutant mice with deletion of the FAAH gene. Null mutant mice showed higher preference for alcohol and voluntarily consumed more alcohol than wild-type littermates. There was no significant difference in consumption of sweet or bitter solutions. To determine the specificity of FAAH for ethanol intake, we studied additional ethanol-related behaviors. There were no differences between null mutant and wild-type mice in severity of ethanol-induced acute withdrawal, conditioned taste aversion to alcohol, conditioned place preference, or sensitivity to hypnotic effect of ethanol. However, null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol. All three behavioral phenotypes (increased preference for ethanol, decreased sensitivity to ethanol-induced sedation, and faster recovery from ethanol-induced motor incoordination) seen in mutant mice were reproduced in wild-type mice by injection of a specific inhibitor of FAAH activity—URB597. These data suggest that increased endocannabinoid signaling increased ethanol consumption owing to decreased acute ethanol intoxication.