The neuronal function of CB2 cannabinoid receptors (CB2Rs) has been less investigated for central nervous system function, because CB2Rs were thought to be predominantly in immune cells in the periphery and were called peripheral CB2Rs. The available CB2R gene knock (KO) mice are partial KO mice that are not suitable for tissue- and cell-type specific behavioral, molecular and pharmacological studies. The purpose of this study is to determine the functional role(s) of CB2Rs in the nervous and immune system using CB2R conditional knockout (cKO), Cx3cr1-Cnr2 and DAT-Cnr2 mice that we have created and produced, and validated the F2 generation for the deletion of CB2Rs in microglia and dopamine (DA) neurons respectively. In this proposal, we test the hypothesis that CB2Rs expressed in microglia cells and dopamine neurons differentially modulate behavioral responses in the CB2R cKO mice models. This hypothesis will be tested in-vivo and in-vitro in the CB2R cKO mice with the following specific aims including the Institutional objective. 1) determine the behavioral effects and functional role of CB2Rs in the CB2 cKO, Cx3cr1-Cnr2 and DAT-Cnr2 mice and their controls; 2) define the neuro-immuno-activity of CB2Rs in microglia and DA neurons; and 3) provide research training opportunities to students and strengthen research environment at a predominantly undergraduate institution. The results will provide insights into the behavioral effects associated with the modulation of CB2Rs and a mouse model to screen cannabinoids and other classes of drugs for conditions of neuro-immune disorders.
There is increasing global awareness and interest in cannabinoid therapeutics. We propose to use the CB2R cKO, DAT-Cnr2 and Cx3cr1-Cnr2 transgenic mice that we have created to probe the role of CB2Rs, and provide insights into the behavioral effects of CB2R modulation and reveal novel therapeutic targets.
