Effect of Novel Allosteric Modulators of Metabotropic Glutamate Receptors on Drug Self-administration and Relapse: A Review of Preclinical Studies and Their Clinical Implications

Biological Psychiatry
Daniele CaprioliYavin Shaham

Abstract

Results from preclinical rodent studies during the last 20 years implicated glutamate neurotransmission in different brain regions in drug self-administration and rodent models of relapse. These results, along with evidence for drug-induced neuroadaptations in glutamatergic neurons and receptors, suggested that addiction might be treatable by medications that inhibit glutamatergic responses to drugs of abuse, drug-associated cues, and stressors. This idea is supported by findings in rodent and primate models that drug self-administration and relapse are reduced by systemic injections of antagonists of ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3. However, these compounds have not advanced to clinical use because of potential side effects and other factors. This state of affairs has led to the development of positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs) of mGluRs. PAMs and NAMs of mGluRs, either of which can inhibit evoked glutamate release, may be suitable for testing in humans. We reviewed results from recent studies of systemically injected PAMs and NAMs of mGluRs in rodents and monkeys, focusing on whether they reduce drug se...Continue Reading

Citations

Jan 10, 2019·Addiction Biology·David Roura-MartínezAlejandro Higuera-Matas
Mar 21, 2018·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Amna ZehraGene-Jack Wang
Apr 11, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jocelyn M Richard
Dec 13, 2019·Frontiers in Neuroanatomy·Christine IbrahimLeon French
Oct 5, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jun-Tao GaoZheng-Xiong Xi
Feb 14, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shaun Yon-Seng KhooNadia Chaudhri
Oct 8, 2020·Nature Reviews. Neuroscience·Marco VenniroYavin Shaham
Apr 1, 2021·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Jana Ruda-KucerovaYousef Tizabi
Mar 12, 2021·Journal of Neurochemistry·Esi DomiEric Augier
Aug 14, 2021·Translational Psychiatry·Julian Cheron, Alban de Kerchove d'Exaerde

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