Brain CB2 cannabinoid receptors and depression: mice models and human subjects

LLORENTE BERZAL A; CHUA L; BECKMANN ; SCHANZ BN, BENNO R, ISHIGURO H, ARINAMI T, TAGLIAFERRO AP, BRUSCO HA, LIU QR , UHL GR, VIVEROS MP, ONAIVI ES

Washington Convention Center: Hall A-C ; USA

Congreso; 2008 Meeting Society for Neuroscience; 2008

Society for Neuroscience

Cannabinoids, endocannabinoids and marijuana use activate cannabinoid receptors to mediate their biological effects. While the expression of CB1-cannabinoid receptors (CB1-Rs) in the brain and periphery has been well characterized, CB2-Rs have received much less attention. Aspects of the functional neuronal expression of CB2-Rs in the brain, features of the CB2-R gene’s structure, regulation and variation and behavioral effects of CB2-R selective drugs remain poorly characterized. We now provide ultrastructural evidence that CB2-R immunoreactivity is localized largely to postsynaptic elements of substantia nigra and in the CA1 area of the hippocampus. We have tested the hypothesis that CB2-Rs might contribute to anti-depressant-like effects of cannabinoids. We performed force swim testing (FST) and modification of wheel running activity in five mouse strains, including the BTBR mice that have been reported to exhibit autism-like behaviors. The CB2-R antagonist AM630 induced mild anti-depressant-like activity while the agonist, BML-190 provoked depression-like-activities. These results were dose and strain dependent. The effect of CB2-R ligands in the mouse FST and wheel running activity provides further behavioral evidence for the involvement of CB2-Rs in the CNS. Depressed human subjects displayed a higher incidence of the CB2-R Q63R, but not H316Y missense variants. Brain CB2-Rs may thus provide novel targets for the effects of cannabinoids in affective disorders.