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• W2946585706 abstract "Non-selective antagonists of metabotropic glutamate receptor subtypes 2 (mGlu2) and 3 (mGlu3) exert rapid antidepressant-like effects by enhancing prefrontal cortex (PFC) glutamate transmission; however, the receptor subtype contributions and underlying mechanisms remain unclear. Here, we leveraged newly developed negative allosteric modulators (NAMs), transgenic mice, and viral-assisted optogenetics to test the hypothesis that selective inhibition of mGlu2 or mGlu3 potentiates PFC excitatory transmission and confers antidepressant efficacy in preclinical models. We found that systemic treatment with an mGlu2 or mGlu3 NAM rapidly activated biophysically unique PFC pyramidal cell ensembles. Mechanistic studies revealed that mGlu2 and mGlu3 NAMs enhance thalamocortical transmission and inhibit long-term depression by mechanistically distinct presynaptic and postsynaptic actions. Consistent with these actions, systemic treatment with either NAM decreased passive coping and reversed anhedonia in two independent chronic stress models, suggesting that both mGlu2 and mGlu3 NAMs induce antidepressant-like effects through related but divergent mechanisms of action." @default.
• W2946585706 created "2019-05-29" @default.
• W2946585706 creator A5016281292 @default.
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• W2946585706 creator A5077644333 @default.
• W2946585706 creator A5077956800 @default.
• W2946585706 creator A5081450945 @default.
• W2946585706 date "2020-01-01" @default.
• W2946585706 modified "2023-10-12" @default.
• W2946585706 title "mGlu2 and mGlu3 Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects" @default.
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• W2946585706 doi "https://doi.org/10.1016/j.neuron.2019.09.044" @default.
• W2946585706 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6952546" @default.
• W2946585706 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31735403" @default.
• W2946585706 hasPublicationYear "2020" @default.
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