mutagenesis approach in mice was used to investigate CB1R mutants revealing a
neuron subpopulation-specific effect on behavioral and neuroendocrine stress
responses (Steiner et al. 2008 ). We have used the Cre-Lox system to generate cell
type specific CB2 conditional knockout DAT-Cnr2 and Cx3cr1-Cnr2 cKO mice
lacking CB2Rs in dopamine and immune cells respectively. We are continuing
studies in defining the molecular role of CB2Rs in microglia/macrophage and
dopamine neurons.
In Table10.1, we summarize some of the known polymorphisms associated or
not associated withCNR2genes involved in human neurological, mental disorders
and other disease conditions. In the coming era of personalized medicine, genetic
variants and haplotypes inCNR1and CNR2genes associated with obesity or
addiction phenotypes may help to identify specific targets in conditions of eCB
dysfunction (Onaivi 2010). Our previous investigations had defined a number of
features of theCNR1gene’s structure, regulation and variation (Zhang et al. 2004 ),
but many features ofCNR2gene structure, regulation and variation still remain
poorly defined. We and others have now demonstrated and reported that variants of
theCNR1gene are associated with a number of disorders and substance abuse
vulnerability in diverse ethnic groups including, European-American, African-
American and Japanese subjects (Zhang et al. 2004 ). Most strikingly, variants of
CNRgenes co-occur with other genetic variations and share biological suscepti-
bility that underlies comorbidity in most neuropsychiatric disturbances (Palomo
et al. 2007 ). Thus, emerging evidence indicates that the eCB system exerts a
powerful modulatory action on retrograde signaling associated with inhibition of
synaptic transmission (Lovinger 2008 ). Additional data from our group focus on
these recent advances in cannabinoid genomics and the surprising new fundamental
Fig. 10.3 The interaction between the endocannabinoid and endovanilloid systems. The
modulation of TRPV1 and CBRs by capsaicin and anandamide was investigated indicating a
cross-talk between TRPV1 CBRs
10 Cannabinoid CB2 Receptor Mechanism ofCannabis sativaL. 237