Group II metabotropic glutamate receptors within the amygdala regulate fear as assessed with potentiated startle in rats.

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Abstract

The contribution to fear and fear learning of amygdala Group II metabotropic glutamate receptors was examined in rats. Pretest intra-amygdala infusions of the Group II receptor agonist LY354740 (0.3 or 1.0 microg/side) significantly disrupted fear-potentiated startle. The same rats were unimpaired when later tested without drug. The Group II receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (3.0 microg/side) mimicked the effect of LY354740, and coadministration of the Group II receptor antagonist LY341495 (0.3 microg/side) prevented it. Pretraining LY354740 (0.3 microg/side) infusions also blocked learning. The effects on learning and performance were significantly less pronounced in rats with misplaced cannulas. Thus, Group II metabotropic receptors within or very near the amygdala regulate fear and fear learning and are a potential target for anxiolytic compounds.

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Pharmacological agents acting at subtypes of metabotropic glutamate receptors.

Darryle D Schoepp, David Jane, James A Monn (1999)

Metabotropic (G-protein-coupled) glutamate (mGlu) receptors have now emerged as a recognized, but still relatively new area of excitatory amino acid research. Current understanding of the roles and involvement of mGlu receptor subtypes in physiological/pathophysiological functions of the central nervous system has been recently propelled by the emergence of various structurally novel, potent, and mGlu receptor selective pharmacological agents. This article reviews the evolution of pharmacological agents that have been reported to target mGlu receptors, with a focus on the known receptor subtype selectivities of current agents.