Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans.
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.
Ishiguro
H
H
Department of Medical Genetics, Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. hishigur@md.tsukuba.ac.jp
Iwasaki
S
S
Teasenfitz
L
L
Higuchi
S
S
Horiuchi
Y
Y
Saito
T
T
Arinami
T
T
Onaivi
E S
ES
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007564:Japan; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D016017:Odds Ratio; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012054:Reinforcement, Psychology; D018570:Risk Assessment; D012307:Risk Factors; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism
D002492:Central Nervous System Depressants; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; D000431:Ethanol; C094023:iodopravadoline; C402944:JHW 015