Antidepressant Effects and Mechanisms of Group II mGlu Receptor-Specific Negative Allosteric Modulators

In this issue of Neuron, Joffe et al. (2020) assess the antidepressant-relevant effects and underlying neural mechanisms of negative allosteric modulators selective for either metabotropic glutamate receptors 2 (mGlu2) or 3 (mGlu3). Negative modulation of both receptors enhanced excitatory glutamatergic input to mouse prefrontal cortex pyramidal cells, leading to antidepressant-relevant actions.