Title:Metabotropic Glutamate Receptor 7: From Synaptic Function to Therapeutic Implications
VOLUME: 14 ISSUE: 5
Author(s):Enza Palazzo, Ida Marabese, Vito de Novellis, Francesco Rossi and Sabatino Maione
Affiliation:Department of Anesthesiology, Surgery and Emergency, The Second University of Naples, Piazza Luigi Miraglia 2, 80138 Naples, Italy.
Keywords:Affective and cognitive behavior, mGluR7 knockout mice phenotype, mGluR7, pain, selective mGluR7 allosteric
modulators, stress response.
Abstract:Metabotropic glutamate receptor 7 (mGluR7) is localized presynaptically at the active zone
of neurotransmitter release. Unlike mGluR4 and mGluR8, which share mGluR7’s presynaptic
location, mGluR7 shows low affinity for glutamate and is activated only by high glutamate
concentrations. Its wide distribution in the central nervous system (CNS) and evolutionary
conservation across species suggest that mGluR7 plays a primary role in controlling excitatory
synapse function. High mGluR7 expression has been observed in several brain regions that are critical
for CNS functioning and are involved in neurological and psychiatric disorder development. Until the recent discovery of
selective ligands for mGluR7, techniques to elucidate its role in neural function were limited to the use of knockout mice
and gene silencing. Studies using these two techniques have revealed that mGluR7 modulates emotionality, stress and fear
responses. N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082) was reported as the first selective mGluR7
allosteric agonist. Pharmacological effects of AMN082 have not completely confirmed the mGluR7-knockout mouse
phenotype; this has been attributed to rapid receptor internalization after drug treatment and to the drug’s apparent lack of
in vivo selectivity. Therefore, the more recently developed mGluR7 negative allosteric modulators (NAMs) are crucial for
understanding mGluR7 function and for exploiting its potential as a target for therapeutic interventions. This review
presents the main findings regarding mGluR7’s effect on modulation of synaptic function and its role in normal CNS
function and in models of neurologic and psychiatric disorders.
