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Signaling pathways responsible for the rapid anti-depressant effects of a GluN2A-preferring NMDA receptor antagonist

Gordillo-Sala, Marta and Auberson, Yves and Adell, Albert (2018) Signaling pathways responsible for the rapid anti-depressant effects of a GluN2A-preferring NMDA receptor antagonist. Translational psychiatry. ISSN 2158-3188

Abstract

In a previous study we found that the selective GluN2A receptor antagonist, NVP-AAM077, elicited rapid antidepressant-like effects in the forced swim test that was related to the release of glutamate and serotonin in the medial prefrontal cortex. In the present work we sought to examine the duration of this behavioral effect as well as the molecular readouts involved. Our results showed that NVP-AAM077 reduced the immobility in the forced swim test 30 min and 24 h after its administration. However, this effect waned 7 days later. The rapid antidepressant-like response was associated with increases in the GluA1 subunit of α-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, mammalian target of rapamycin (mTOR) signaling and glia markers such as glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter 1 (EAAT1) in the medial prefrontal cortex. In contrast, the prolonged antidepressant-like effects of NVP-AAM077 are possibly associated with increases in BDNF and p11.

Item Type: Article
Date Deposited: 19 Jun 2018 00:45
Last Modified: 19 Jun 2018 00:45
URI: https://oak.novartis.com/id/eprint/34184

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