Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice.
Previous studies have shown that mice lacking cannabinoid (CB1) receptor gene consume markedly reduced levels of ethanol. Mice lacking the enzyme fatty acid amidohydrolase (FAAH) are severely impaired in their ability to degrade anandamide (AEA) and therefore represent a unique animal model in which to examine the function of AEA in vivo on ethanol-drinking behavior. In the current study, FAAH(-/-) mice were tested for ethanol, saccharin or quinine consumption and preference. Ethanol-induced hypothermia, and sleep time were used to evaluate the sensitivity to acute effects of ethanol. Ethanol intake and preference were increased only in female FAAH(-/-) mice. No significant difference in saccharin or quinine consumption or preference was observed between genotypes. Female FAAH(-/-) mice were less sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol. Supersensitivity to exogenous AEA was noted in both male and female FAAH(-/-) mice. Following voluntary ethanol consumption, CB1 receptor levels and function were down-regulated in male FAAH(+/+), FAAH(-/-), and female FAAH(+/+) mice but not in female FAAH(-/-) mice. Our results suggest that absence of an effect in male mice indicates a sex-linked mechanism that is secondary (or modulatory) to FAAH function. Thus, the data suggest that FAAH may be indirectly related to ethanol intake and sensitivity and central endocannabinoidergic-mediated pathways may regulate ethanol consumption.
Basavarajappa
Balapal S
BS
Division of Analytical Psychopharmacology, New York State Psychiatric Institute, USA. basavaraj@nki.rfmh.org
Yalamanchili
Ratnakumar
R
Cravatt
Benjamin F
BF
Cooper
Thomas B
TB
Hungund
Basalingappa L
BL
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012727:Sex Characteristics; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000431:Ethanol; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases