Brain cannabinoid CB2 receptors modulate cocaine's actions in mice

作者：Xi Zheng Xiong^*; Peng Xiao Qing; Li Xia; Song Rui; Zhang Hai Ying; Liu Qing Rong; Yang Hong Ju; Bi Guo Hua; Li Jie; Gardner Eliot L

来源：Nature Neuroscience, 2011, 14(9): 1160-U216.

DOI：10.1038/nn.2874

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 (CB1-/-, also known as Cnr1(-/-)) mice, but not in CB2-/-(Cnr2(-/-)) mice. This inhibition was mimicked by GW405833, another CB2 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 CB1-/- 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 CB2 receptors modulate cocaine's rewarding and locomotor-stimulating effects, likely by a dopamine-dependent mechanism.

• 出版日期2011-9