Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

Hai Ying Zhang, Ming Gao, Qing Rong Liu, Guo Hua Bi, Xia Li, Hong Ju Yang, Eliot L. Gardner, Jie Wu, Zheng Xiong Xi

Research output: Contribution to journalArticlepeer-review

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 inWT 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.

Original languageEnglish (US)
Pages (from-to)E5007-E5015
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number46
DOIs
StatePublished - Nov 18 2014

ASJC Scopus subject areas

  • General

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