biostudies-literatureDogra SACADIA PharmaceuticalsNIMH NIH HHSBoehringer IngelheimNINDS NIH HHSNational Institutes of Health173493https://www.ebi.ac.uk/biostudies/studies/S-EPMC9729465biostudies-literatureUnknown221Glutamate 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.Pharmacology, biochemistry, and behaviorMetabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.PMC9729465R01 NS031373R01NS031373R01MH062646R01 MH074953R01 MH119673R01 MH062646Putnam JConn PJDogra SfalseMetabotropic 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.2022-01-01T00:00:00Z2022 Nov2025-04-19T18:35:11.593Z2025-04-19T18:35:11.593ZS-EPMC97294653640224310.1016/j.pbb.2022.173493