Brain cannabinoid CB2 receptors modulate cocaine's actions in mice

Zheng Xiong Xi, Xiao Qing Peng, Xia Li, Rui Song, Hai Ying Zhang, Qing Rong Liu, Hong Ju Yang, Guo Hua Bi, Jie Li, Eliot L. Gardner

Research output: Contribution to journalArticlepeer-review

268 Scopus citations


The presence and function of cannabinoid CB2 receptors in the brain have been the subjects of much debate. We found that systemic, intranasal or intra-accumbens local administration of JWH133, a selective CB2 receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion, and cocaine-enhanced accumbens extracellular dopamine in wild-type and CB1 receptor knockout (CB 1 also known as Cnr1 mice, but not in CB2 (Cnr2 ) mice. This inhibition was mimicked by GW405833, another CB 2 receptor agonist with a different chemical structure, and was blocked by AM630, a selective CB2 receptor antagonist. Intra-accumbens administration of JWH133 alone dose-dependently decreased, whereas intra-accumbens administration of AM630 elevated, extracellular dopamine and locomotion in wild-type and CB 1 mice, but not in CB2 mice. Intra-accumbens administration of AM630 also blocked the reduction in cocaine self-administration and extracellular dopamine produced by systemic administration of JWH133. These findings suggest that brain CB 2 receptors modulate cocaine's rewarding and locomotor-stimulating effects, likely by a dopamine-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)1160-1168
Number of pages9
JournalNature neuroscience
Issue number9
StatePublished - Sep 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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