Effects of the absence of TRPV1 in the expression of the cannabinoid 1 (CB1) receptor in the brain

Abstract

[EN] Though cannabinoids functions in the brain are typically associated with the activation of cannabinoid receptor 1 (CB1R), several effects depend on the activation of TRPV1, a receptor from the transient receptor potential channel family involved in synaptic transmission, plasticity and some pathologies. An anatomical arrangement between CB1R and TRPV1 in various regions of the brain has been demonstrated, which allows a complex, but currently largely unidentified, crosstalk that involves activation of both TRPV1 and CB1R by anandamide. The constitutive absence of TRPV1 change the expression and localization of components of the endocannabinoid system (ECS), including CB1R, in the hippocampus, though it is currently unknown whether these changes occur in other regions of the brain. This research aims to analyze the impact of the lack of TRPV1 on the ECS’s physical and molecular changes with particular attention to the CB1R in the amygdala, hippocampus, substantia nigra, globus pallidus, retrospenial cortex, cingulate area, motor cortex, olfactory bulb and cerebellum. For this purpose, using avidin-biotin complex immunohistochemistry techniques and light microscopy, the expression and localization of CB1R was studied in a mouse model with the genetic deletion of TRPV1 compared to wild-type mice. A significant increase in CB1R density was observed in the retrosplenial cortex, and a decrease in the cingulate area, motor cortex, and cerebellum upon the constitutive deletion of the TRPV1 gene, supporting the hypothesis of a reciprocal relation between both systems, so the lack of TRPV1 could lead to compensatory processes affecting the expression and localization of the ECS.