Metabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.

Glutamate is a major excitatory neurotransmitter in the central nervous system (CNS) and abnormalities in the glutamatergic system underlie various CNS disorders. As metabotropic glutamate receptor 3 (mGlu3 receptor) regulates glutamatergic transmission in various brain areas, emerging literature suggests that targeting mGlu3 receptors can be a novel approach to the treatment of psychiatric and neurological disorders. For example, mGlu3 receptor negative allosteric modulators (NAMs) induce rapid antidepressant-like effects in both acute and chronic stress models. Activation of mGlu3 receptors can enhance cognition in the rodents modeling schizophrenia-like pathophysiology. The mGlu3 receptors expressed in the astrocytes induce neuroprotective effects. Although polymorphisms in GRM3 have been shown to be associated with addiction, there is not significant evidence about the efficacy of mGlu3 receptor ligands in rodent models of addiction. Collectively, drugs targeting mGlu3 receptors may provide an alternative approach to fill the unmet clinical need for safer and more efficacious therapeutics for CNS disorders.