Sex Differences in the Sustained Effects of Ketamine on Resilience to Chronic Stress.
chronic stress
ketamine
parvalbumin
prefrontal cortex
sex differences
stress resilience and vulnerability
Journal
Frontiers in behavioral neuroscience
ISSN: 1662-5153
Titre abrégé: Front Behav Neurosci
Pays: Switzerland
ID NLM: 101477952
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
07
2020
accepted:
18
09
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
17
11
2020
Statut:
epublish
Résumé
Exposure to stress is recognized to be a triggering factor in several mood disorders, including depression and anxiety. There is very little understanding of why female subjects have a significantly higher risk for these conditions than males. Recent findings in male rodents indicated that prophylactic ketamine can prevent the development of a stress-induced depressive-like phenotype, providing a pharmacological tool to study the mechanisms underlying stress resilience. Unfortunately, none of these studies incorporated female subjects, nor did they provide a mechanistic understanding of the effects of ketamine on stress resilience. Our previous work identified the prefrontal glutamatergic and parvalbumin (PV) systems as potential molecular mechanisms underlying sex differences in susceptibility to stress-induced emotional deregulations. To further address this point, we treated male and female mice with a single dose of ketamine before exposure to a chronic stress paradigm to determine whether stress-resilience induced by a pre-exposure to ketamine is similar in males and females and whether modulation of the prefrontal glutamatergic and PV systems by ketamine is associated with these behavioral effects. Ketamine prevented chronic stress-induced changes in behaviors in males, which was associated with a reduction in expression of PV and the NMDA receptor NR1 subunit. Ketamine did not protect females against the effects of chronic stress and did not change significantly prefrontal gene expression. Our data highlight fundamental sex differences in the sustained effects of ketamine. They also further implicate prefrontal glutamatergic transmission and PV in resilience to chronic stress.
Identifiants
pubmed: 33192367
doi: 10.3389/fnbeh.2020.581360
pmc: PMC7606988
doi:
Types de publication
Journal Article
Langues
eng
Pagination
581360Subventions
Organisme : NIMH NIH HHS
ID : R21 MH119090
Pays : United States
Informations de copyright
Copyright © 2020 Okine, Shepard, Lemanski and Coutellier.
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