mGlu5: A double-edged sword for aversive learning related therapeutics

Author:

Tan Shawn Zheng Kai12ORCID,Kim Jee Hyun3ORCID

Affiliation:

1. School of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong

2. European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridgeshire, United Kingdom

3. IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia

Abstract

Aversive memories underlie many types of anxiety disorders. One area of research to more effectively treat anxiety disorders has therefore been identifying pharmacological targets to affect memory processes. Among these targets, the metabotropic glutamate 5 receptor (mGlu5) has received attention due to the availability of drugs to utilize its role in learning and memory. In this review, we highlight preclinical studies examining the role of mGlu5 at various stages of aversive learning and its inhibition via extinction in order to gain a better understanding of its therapeutic potential. We suggest that mGlu5 has distinct roles at different stages of memory that not only makes it a tricky target, but a double-edged sword as a therapeutic. However, the selective involvement of mGlu5 in different memory stages allows for certain precision that could be harnessed clinically. We therefore suggest potential applications, limitations, and pitfalls when considering use of mGlu5 modulators as therapeutics. In addition, we recommend future studies to address important gaps in this literature, such as sex and age factors in light of anxiety disorders being more prevalent in those demographics.

Publisher

Episteme Health Inc

Subject

General Medicine

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