title: Brain cannabinoid CB₂ receptors modulate cocaine's actions in mice.
abstract: The presence and function of cannabinoid CB(2) 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 CB(2) receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion, and cocaine-enhanced accumbens extracellular dopamine in wild-type and CB(1) receptor knockout (CB(1)(-/-), also known as Cnr1(-/-)) mice, but not in CB(2)(-/-) (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 CB(2) 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 CB(2)(-/-) 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.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA. zxi@intra.nida.nih.gov
authors.forename: Zheng-Xiong
authors.initials: ZX
authors.lastname: Xi
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Peng
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Yang
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Bi
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
mesh_terms: D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002186:Cannabinoids / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D045442:Rotarod Performance Test / Q000379:methods; D012646:Self Administration
chemical_list: D002186:Cannabinoids; D018765:Dopamine Uptake Inhibitors; D007211:Indoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D003042:Cocaine; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline