Interactions between metabotropic glutamate and CB1 receptors: implications for mood, cognition, and synaptic signaling based on data from mGluR and CB1R-targeting drugs.

Metabotropic glutamate receptors (mGluRs) are part of the G protein-coupled receptors (GPCRs) family. They are coupled to G_αq (group I) or G_i/o (groups II and III) proteins, which result in the generation of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP₃) or the inhibition of adenylyl cyclase, respectively. mGluRs have been implicated in anxiety, depression, learning, and synaptic plasticity. Similarly, CB1 cannabinoid receptors (CB1Rs), also GPCRs, play roles in cognitive function and mood regulation through G_αi/o-mediated inhibition of adenylyl cyclase. Both mGluRs and CB1Rs exhibit surface labeling and undergo endocytosis. Given the similar cellular distribution and mechanisms of action, this review complies with fundamental data on the potential interactions and mutual regulation of mGluRs and CB1Rs in the context of depression, anxiety, and cognition, providing pioneering insights into their interplay.