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Involvement of Endocannabinoids in Alcohol “Binge” Drinking: Studies of Mice with Human Fatty Acid Amide Hydrolase Genetic Variation and After CB 1 Receptor Antagonists
Author(s) -
Zhou Yan,
Huang Ted,
Lee Francis,
Kreek Mary Jeanne
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12989
Subject(s) - fatty acid amide hydrolase , endocannabinoid system , cannabinoid receptor , alcohol , binge drinking , chemistry , receptor , amide , genetic variation , variation (astronomy) , anandamide , cannabinoid , fatty acid , gene , biochemistry , antagonist , alcohol consumption , physics , astrophysics
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 C 385 A 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 C 385 A 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 CB 1 receptor antagonist AM 251 reduced alcohol intake in the wild‐type mice. Conclusions These data suggest that there is direct and selective involvement of the human FAAH C 385 A SNP and CB 1 receptors in alcohol “binge” drinking.