Molecular and cellular dissection of NMDA receptor subtypes as antidepressant targets

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. Howe...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Lang, Elisabeth (VerfasserIn) , Sprengel, Rolf (VerfasserIn) , Gass, Peter (VerfasserIn) , Inta, Dragos (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2018
In: Neuroscience & biobehavioral reviews
Year: 2017, Jahrgang: 84, Pages: 352-358
ISSN:1873-7528
DOI:10.1016/j.neubiorev.2017.08.012
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.neubiorev.2017.08.012
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0149763417303226
Volltext
Verfasserangaben:Elisabeth Lang, Anne S. Mallien, Andrei-Nicolae Vasilescu, Dimitri Hefter, Alessia Luoni, Marco A. Riva, Stefan Borgwardt, Rolf Sprengel, Undine E. Lang, Peter Gass, Dragos Inta
Beschreibung
Zusammenfassung: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.
Beschreibung:Available online 23 August 2017
Gesehen am 15.10.2018
Beschreibung:Online Resource
ISSN:1873-7528
DOI:10.1016/j.neubiorev.2017.08.012