Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques

Abstract Chronic psychosocial stress is associated with increased risk of psychiatric disorders. Magnetic resonance spectroscopy (MRS) in humans has been used to show that glutamate levels in medial prefrontal cortex (mPFC) following acute stress exposure adapt to recent chronic stress levels. Here,...

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Main Authors: Michael T. Treadway, Samantha A. Betters, Jessica A. Cooper, Chun-Xia Li, Xiaodong Zhang, Vasiliki Michopoulos
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03334-2
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author Michael T. Treadway
Samantha A. Betters
Jessica A. Cooper
Chun-Xia Li
Xiaodong Zhang
Vasiliki Michopoulos
author_facet Michael T. Treadway
Samantha A. Betters
Jessica A. Cooper
Chun-Xia Li
Xiaodong Zhang
Vasiliki Michopoulos
author_sort Michael T. Treadway
collection DOAJ
description Abstract Chronic psychosocial stress is associated with increased risk of psychiatric disorders. Magnetic resonance spectroscopy (MRS) in humans has been used to show that glutamate levels in medial prefrontal cortex (mPFC) following acute stress exposure adapt to recent chronic stress levels. Here, we sought to determine the presence of this glutamate stress response adaptation in rhesus macaques, whose societies are maintained by dominance relationships that are enforced by agonistic interactions and result in chronic stress phenotypes seen in humans. We tested the hypothesis that change in mPFC glutamate after an acute stressor would be moderated by behavioral factors related to social subordination in a manner similar to that previously observed in humans. Seventeen adult female rhesus monkeys (Macaca mulatta, 13–23 yrs.) were observed over ten weeks to collect behavioral data and then received two MRS scans. The first scan occurred after acute stress manipulation involving relocation and isolation. The second control scan occurred after acclimation to the new location. As expected, we found that a behavioral measure of social subordination predicted an adaptive glutamate response such that animals experiencing more submissive behavior asymmetry (a behavioral measure related to social subordination) exhibited an attenuated glutamate response to the acute stressor. These data establish the use of MRS to measure the adaptive glutamate stress in non-human primates and will help further our understanding of the neurobiology of stress adaptation.
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spelling doaj-art-22012e37e78b49a5be898fd740b4e78f2025-08-20T03:40:50ZengNature Publishing GroupTranslational Psychiatry2158-31882025-03-011511910.1038/s41398-025-03334-2Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaquesMichael T. Treadway0Samantha A. Betters1Jessica A. Cooper2Chun-Xia Li3Xiaodong Zhang4Vasiliki Michopoulos5Department of Psychology, Emory UniversityDepartment of Psychology, Emory UniversityDepartment of Psychiatry and Behavioral Sciences, Emory School of MedicineEmory National Primate Research CenterEmory National Primate Research CenterDepartment of Psychiatry and Behavioral Sciences, Emory School of MedicineAbstract Chronic psychosocial stress is associated with increased risk of psychiatric disorders. Magnetic resonance spectroscopy (MRS) in humans has been used to show that glutamate levels in medial prefrontal cortex (mPFC) following acute stress exposure adapt to recent chronic stress levels. Here, we sought to determine the presence of this glutamate stress response adaptation in rhesus macaques, whose societies are maintained by dominance relationships that are enforced by agonistic interactions and result in chronic stress phenotypes seen in humans. We tested the hypothesis that change in mPFC glutamate after an acute stressor would be moderated by behavioral factors related to social subordination in a manner similar to that previously observed in humans. Seventeen adult female rhesus monkeys (Macaca mulatta, 13–23 yrs.) were observed over ten weeks to collect behavioral data and then received two MRS scans. The first scan occurred after acute stress manipulation involving relocation and isolation. The second control scan occurred after acclimation to the new location. As expected, we found that a behavioral measure of social subordination predicted an adaptive glutamate response such that animals experiencing more submissive behavior asymmetry (a behavioral measure related to social subordination) exhibited an attenuated glutamate response to the acute stressor. These data establish the use of MRS to measure the adaptive glutamate stress in non-human primates and will help further our understanding of the neurobiology of stress adaptation.https://doi.org/10.1038/s41398-025-03334-2
spellingShingle Michael T. Treadway
Samantha A. Betters
Jessica A. Cooper
Chun-Xia Li
Xiaodong Zhang
Vasiliki Michopoulos
Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
Translational Psychiatry
title Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
title_full Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
title_fullStr Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
title_full_unstemmed Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
title_short Medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
title_sort medial prefrontal glutamate response to acute stress is associated with social subordination in female rhesus macaques
url https://doi.org/10.1038/s41398-025-03334-2
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