{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:49:10Z","timestamp":1790930950300,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,10,6]],"date-time":"2008-10-06T00:00:00Z","timestamp":1223251200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:p>Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2\u2010Rs) in healthy brains, but CB2\u2010R expression has been demonstrated in rat microglial cells and other brain\u2010associated cells during inflammation. Thus, neuronal expression of CB2\u2010Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the<jats:italic>CB2<\/jats:italic>gene might be associated with depression in a human population and that alteration in<jats:italic>CB2<\/jats:italic>gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the<jats:italic>CB2<\/jats:italic>gene was found in Japanese depressed subjects. CB2\u2010Rs and their gene transcripts are expressed in the brains of na\u00efve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced<jats:italic>CB2<\/jats:italic>gene expression, and chronic treatment with JWH015 a putative CB2\u2010R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus\u2010maze test, indicating the functional presence of CB2\u2010Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2\u2010Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2\u2010Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity.<\/jats:p>","DOI":"10.1196\/annals.1432.036","type":"journal-article","created":{"date-parts":[[2009,8,11]],"date-time":"2009-08-11T11:47:03Z","timestamp":1249991223000},"page":"434-449","source":"Crossref","is-referenced-by-count":157,"title":["Functional Expression of Brain Neuronal CB2 Cannabinoid Receptors Are Involved in the Effects of Drugs of Abuse and in Depression"],"prefix":"10.1196","volume":"1139","author":[{"given":"Emmanuel S.","family":"Onaivi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Ping","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejal","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Meozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lester","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Perchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoila","family":"Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Tagliaferro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Brusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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