Abstract

The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein–coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gα_q/11 proteins and display an excitatory response upon activation, whereas the cannabinoid type 1 receptor, mainly present at presynaptic terminals, is coupled to the G_i/o protein and triggers an inhibitory response. Recent studies suggest that the glutamatergic and endocannabinoid systems exhibit a functional interaction to modulate several neural processes. In this review, we discuss possible mechanisms involved in this crosstalk and its relationship with physiologic and pathologic conditions, including nociception, addiction, and fragile X syndrome.