Serotonin and Glutamate Interactions in Preclinical Schizophrenia Models.

ACS Chemical Neuroscience
Urjita H Shah, Javier González-Maeso

Abstract

The serotonergic and glutamatergic neurotransmitter systems have both been implicated in the pathophysiology of schizophrenia, and there are multiple lines of evidence to demonstrate that they can interact in a functionally relevant manner. Particularly, it has been demonstrated that serotonin (5-hydroxytryptamine) 2A (5-HT2A) receptors and metabotropic glutamate type 2 (mGlu2) receptors can assemble into a functional heteromeric complex and modulate each other's function. This heteromeric complex has been implicated in the mechanism of action of hallucinogens as well as antipsychotic agents, and its role has been demonstrated in both in vitro and in vivo systems. Additionally, the difference in the changes in Gi/o and Gq/11 protein activity when a ligand binds to the heteromeric complex can be used as an index to predict the pro- or antipsychotic properties of an agent. Signaling via the heteromer is dysregulated in postmortem human brain samples of schizophrenia subjects, which may be linked to altered cortical functions. Alternative routes for the functional crosstalk between mGlu2 and 5-HT2A receptors include synaptic and epigenetic mechanisms. This Review highlights the advances made over the past few years in elucidating ...Continue Reading

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Nov 26, 2020·International Journal of Molecular Sciences·Paulina Cieślik, Joanna M Wierońska
Nov 17, 2020·Frontiers in Cellular Neuroscience·Jon DelaCuesta-BarrutiaAmaia M Erdozain
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Jul 2, 2021·Frontiers in Physiology·Xiaoxu YangJingyu Xu
Jun 12, 2020·Neuropharmacology·Trevor Sharp, Nicholas M Barnes

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