Molecular and cellular dissection of NMDA receptor subtypes as antidepressant targets

• Verfasst von: Lang, Elisabeth [VerfasserIn]
• Verfasst von: Sprengel, Rolf [VerfasserIn]
• Verfasst von: Gass, Peter [VerfasserIn]
• Verfasst von: Inta, Dragos [VerfasserIn]
• Titel: Molecular and cellular dissection of NMDA receptor subtypes as antidepressant targets
• Verf.angabe: 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
• Jahr: 2018
• Jahr des Originals: 2017
• Umfang: 7 S.
• Fussnoten: Available online 23 August 2017 ; Gesehen am 15.10.2018
• Titel Quelle: Enthalten in: Neuroscience & biobehavioral reviews
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1978
• Jahr Quelle: 2018
• Band/Heft Quelle: 84(2018), Seite 352-358
• ISSN Quelle: 1873-7528
• DOI: doi:10.1016/j.neubiorev.2017.08.012
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Depression
• Sach-SW: GluN2 subunits
• Sach-SW: Glutamate
• Sach-SW: Ketamine
• Sach-SW: Molecular biology
• Sach-SW: NMDA receptors
• K10plus-PPN: 1581908571

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.