MGlu₂ and mGlu₃ Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects.

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 m

SUBMITTER: Joffe ME 

PROVIDER: S-EPMC6952546 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature