Ethanol preferring rats have decreased expression and activity of the endocannabinoid degrading enzyme, fatty acid amidolydrolase (FAAH), increased endocannabinoid levels, and decreased endocannabinoid receptors (CB1) and receptor coupling in prefrontal cortex. A CB1 antagonist decreases and a FAAH inhibitor increases ethanol responding.Rats were bidirectionally bred for high and low ethanol preference for over 90 generations. Changes in FAAH expression and activity, endocannabinoid levels, and CB1 receptor density and coupling were not found in striatum or cerebellum. Doseresponse curves were obtained for the CB1 antagonist SR141716A given intraperitoneally or through microinjection into the prefrontal cortex and for the FAAH inhibitor URB597 microinjected into prefrontal cortex, only highest dose is shown. FAH expression measured in total RNA with PCR. CB1 expression was not different between the ethanol preferring and nonpreferring rats. (Constructed from data in Hansson, A.C. et al. Neuropsychopharmacology, 32: 117, 2007) ©2007 NBEP