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Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans

Abstract

We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. Mice experiencing more alcohol preference by drinking showed reduced Cb2 gene expression, whereas mice with little preference showed no changes of it in ventral midbrain. Alcohol preference in conjunction with chronic mild stress were enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic stress, whereas antagonist AM630 prevented development of alcohol preference. There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population (P=0.007; odds ratio 1.25, 95% CI, (1.06–1.47)). CB2 under such environment is associated with the physiologic effects of alcohol and CB2 antagonists may have potential as therapies for alcoholism.

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Abbreviations

CB2:

cannabinoid type 2 receptor

CNR:

cannabinoid receptor

CMS:

chronic mild stress

CNS:

central nervous system

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Acknowledgements

This work was supported financially by Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Science and Technology. Also it was supported by William Paterson, University Center for research and Dean, Dr Sandra DeYoung, who provided student worker support for the maintenance of laboratory animals. We also thank Dr Scott Hall (National Institutes of Health, National Institute on Drug Abuse) for technical advice regarding generation of a mouse model of alcohol preference and brain anatomy.

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Correspondence to H Ishiguro.

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Ishiguro, H., Iwasaki, S., Teasenfitz, L. et al. Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans. Pharmacogenomics J 7, 380–385 (2007). https://doi.org/10.1038/sj.tpj.6500431

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