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Neurosci Biobehav Rev. 2018 Jan;84:352-358. doi: 10.1016/j.neubiorev.2017.08.012. Epub 2017 Aug 23.

Molecular and cellular dissection of NMDA receptor subtypes as antidepressant targets.

Author information

1
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
2
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
3
Department of Psychiatry (UPK), University of Basel, Switzerland.
4
Max-Planck Research Group at the Institute for Anatomy and Cell Biology, Heidelberg University, Germany.
5
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Department of Psychiatry (UPK), University of Basel, Switzerland. Electronic address: Dragos.Inta@upkbs.ch.

Abstract

A growing body of evidence supports the idea that drugs targeting the glutamate system may represent a valuable therapeutic alternative in major depressive disorders (MDD). The rapid and prolonged mood elevating effect of the NMDA receptor (NMDAR) antagonist ketamine has been studied intensely. However, its clinical use is hampered by deleterious side-effects, such as psychosis. Therefore, a better understanding of the mechanisms of the psychotropic effects after NMDAR blockade is necessary to develop glutamatergic antidepressants with improved therapeutic profile. Here we review recent experimental data that addressed molecular/cellular determinants of the antidepressant effect mediated by inactivating NMDAR subtypes. We refer to results obtained both in pharmacological and genetic animal models, ranging from global to conditional NMDAR manipulation. Our main focus is on the contribution of different NMDAR subtypes to the psychoactive effects induced by NMDAR ablation/blockade. We review data analyzing the effect of NMDAR subtype deletions limited to specific neuronal populations/brain areas in the regulation of mood. Altogether, these studies suggest effective and putative specific NMDAR drug targets for MDD treatment.

KEYWORDS:

Depression; GluN2 subunits; Glutamate; Ketamine; Molecular biology; NMDA receptors

PMID:
28843752
DOI:
10.1016/j.neubiorev.2017.08.012
[Indexed for MEDLINE]

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