title: Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice.
abstract: Cannabinoid CB2 receptors (CB2Rs) have been recently reported to modulate brain dopamine (DA)-related behaviors; however, the cellular mechanisms underlying these actions are unclear. Here we report that CB2Rs are expressed in ventral tegmental area (VTA) DA neurons and functionally modulate DA neuronal excitability and DA-related behavior. In situ hybridization and immunohistochemical assays detected CB2 mRNA and CB2R immunostaining in VTA DA neurons. Electrophysiological studies demonstrated that activation of CB2Rs by JWH133 or other CB2R agonists inhibited VTA DA neuronal firing in vivo and ex vivo, whereas microinjections of JWH133 into the VTA inhibited cocaine self-administration. Importantly, all of the above findings observed in WT or CB1(-/-) mice are blocked by CB2R antagonist and absent in CB2(-/-) mice. These data suggest that CB2R-mediated reduction of VTA DA neuronal activity may underlie JWH133's modulation of DA-regulated behaviors.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013;
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Bi
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA 92093;
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
authors.affiliation: Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013; Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004; and Department of Physiology, Shantou University Medical College, Shantou, Guangdong 210854, China zxi@intra.nida.nih.gov jie.wu@dignityhealth.org.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224; zxi@intra.nida.nih.gov jie.wu@dignityhealth.org.
authors.forename: Zheng-Xiong
authors.identifier: http://orcid.org/0000-0001-6482-8104
authors.initials: ZX
authors.lastname: Xi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012201:Reward; D012646:Self Administration; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D002186:Cannabinoids; D007211:Indoles; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D003042:Cocaine; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline; D004298:Dopamine
keywords: CB2 receptor; JWH133; cannabinoid; cocaine; dopamine