title: Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.
abstract: BACKGROUND
  Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown.
  
  
  RESULTS
  In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 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 CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain.
  
  
  CONCLUSIONS
  Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.
authors.affiliation: Department of Biology, William Paterson University, Wayne, New Jersey, USA. OnaiviE@wpunj.edu
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Onaivi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Gong
authors.forename: Sejal
authors.initials: S
authors.lastname: Patel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Meozzi
authors.forename: Lester
authors.initials: L
authors.lastname: Myers
authors.forename: Alex
authors.initials: A
authors.lastname: Perchuk
authors.forename: Zoila
authors.initials: Z
authors.lastname: Mora
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Tagliaferro
authors.forename: Eileen
authors.initials: E
authors.lastname: Gardner
authors.forename: Alicia
authors.initials: A
authors.lastname: Brusco
authors.forename: B Emmanuel
authors.initials: BE
authors.lastname: Akinshola
authors.forename: Bruce
authors.initials: B
authors.lastname: Hope
authors.forename: Javier
authors.initials: J
authors.lastname: Lujilde
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Shinya
authors.initials: S
authors.lastname: Iwasaki
authors.forename: David
authors.initials: D
authors.lastname: Macharia
authors.forename: Lindsey
authors.initials: L
authors.lastname: Teasenfitz
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D003866:Depressive Disorder / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009474:Neurons / Q000737:chemistry*; D011110:Polymorphism, Genetic; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis* / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics*
chemical_list: D043885:Receptor, Cannabinoid, CB2