Involvement of Endocannabinoids in Alcohol "Binge" Drinking: Studies of Mice with Human Fatty Acid Amide Hydrolase Genetic Variation and After CB1 Receptor Antagonists

Yan Zhou, Ted Huang, Francis Lee, Mary Jeanne Kreek
Alcoholism, Clinical and Experimental Research 2016, 40 (3): 467-73

BACKGROUND: The endocannabinoid system has been found to play an important role in modulating alcohol intake. Inhibition or genetic deletion of fatty acid amide hydrolase (FAAH; a key catabolic enzyme for endocannabinoids) leads to increased alcohol consumption and preference in rodent models. A common human single-nucleotide polymorphism (SNP; C385A, rs324420) in the FAAH gene is associated with decreased enzymatic activity of FAAH, resulting in increased anandamide levels in both humans and FAAH C385A knock-in mice.

METHODS: As this FAAH SNP has been reported to be associated with altered alcohol abuse, the present study used these genetic knock-in mice containing the human SNP C385A to determine the impact of variant FAAH gene on alcohol "binge" drinking in the drinking-in-the-dark (DID) model.

RESULTS: We found that the FAAH(A/A) mice had greater alcohol intake and preference than the wild-type FAAH(C/C) mice, suggesting that increased endocannabinoid signaling in FAAH(A/A) mice led to increased alcohol "binge" consumption. The specificity on alcohol vulnerability was suggested by the lack of any FAAH genotype difference on sucrose or saccharin intake. Using the "binge" DID model, we confirmed that selective CB1 receptor antagonist AM251 reduced alcohol intake in the wild-type mice.

CONCLUSIONS: These data suggest that there is direct and selective involvement of the human FAAH C385A SNP and CB1 receptors in alcohol "binge" drinking.

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