Signaling pathways responsible for the rapid antidepressant-like effects of a GluN2A-preferring NMDA receptor antagonist

In a previous study we found that the preferring 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 duratio...

Full description

Saved in:
Bibliographic Details
Published in:Translational psychiatry 2018-04, Vol.8 (1), p.84-9, Article 84
Main Authors: Gordillo-Salas, Marta, Pilar-Cuéllar, Fuencisla, Auberson, Yves P., Adell, Albert
Format: Article
Language:English
Subjects:
631/154/436
631/378/340
96/1
Animals
Antidepressants
Antidepressive Agents - administration & dosage
Behavior, Animal - drug effects
Behavioral Sciences
Biological Psychology
Brain-Derived Neurotrophic Factor - metabolism
Depression - drug therapy
Male
Medicine
Medicine & Public Health
Neuroglia - drug effects
Neuroglia - metabolism
Neurons - drug effects
Neurons - metabolism
Neurosciences
Pharmacotherapy
Prefrontal Cortex - drug effects
Prefrontal Cortex - metabolism
Psychiatry
Quinoxalines - administration & dosage
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Signal Transduction
Synapses - drug effects
Synapses - metabolism
TOR Serine-Threonine Kinases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In a previous study we found that the preferring 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 seems to be 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, glia markers such as glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter 1 (EAAT1), and a rapid mobilization of intracellular stores of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex.
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-018-0131-9