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Cited by 23Stress Responses and CortisolNeuroendocrine regulation and behaviorMemory and Neural Mechanisms

Gonadal steroid hormone receptors in the medial amygdala contribute to experience-dependent changes in stress vulnerability

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Cooper, Matthew A., Clinard, Catherine T., Dulka, Brooke N., Grizzell, J. Alex, Loewen, Annie L., Campbell, Ashley V., Adler, Samuel G.·2021·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2021.105249PMC PMC8217359
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Abstract

Social experience can generate neural plasticity that changes how individuals respond to stress. Winning aggressive encounters alters how animals respond to future challenges and leads to increased plasma testosterone concentrations and androgen receptor (AR) expression in the social behavior neural network. In this project, our aim was to identify neuroendocrine mechanisms that account for changes in stress-related behavior following the establishment of dominance relationships over a two-week period. We used a Syrian hamster model in which acute social defeat stress increases anxiety-like responses in a conditioned defeat test in males and in a social avoidance test in females. First, we administered flutamide, an AR antagonist, via intraperitoneal injections daily during the establishment of dominance relationships in male hamsters. We found that pharmacological blockade of AR prevented a reduction in conditioned defeat in dominant males and blocked an upregulation of AR in the posterior dorsal medial amygdala (MePD) and posterior ventral medial amygdala (MePV), but not in the ventral lateral septum. Next, we administered flutamide into the posterior aspects of the medial amygdala (MeP) prior to acute social defeat stress or prior to conditioned defeat testing in males. We found that pharmacological blockade of AR in the MeP prior to social defeat, but not prior to testing, increased the conditioned defeat response in dominant males and did not alter behavior in subordinates. Finally, we developed a procedure to establish dominance relationships in female hamsters and investigated status-dependent changes in plasma steroid hormone concentrations, estrogen receptor alpha (ERα) immunoreactivity, and defeat-induced social avoidance. We found that dominant female hamsters showed reduced social avoidance regardless of social defeat exposure as well as increased ERα expression in the MePD, but no status-dependent changes in the concentration of plasma steroid hormones. Overall, these findings suggest that achieving and maintaining stable social dominance leads to sex-specific neural plasticity in the MeP that underlies status-dependent changes in stress vulnerability.

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  • Pharmacological inhibition of AR in the MEA of dominant male hamsters increases sensitivity to social stress.

    “In adult hamsters, dominant males have more androgen receptor expression in the medial amygdala (MEA) than subordinates, and pharmacological inhibition of AR in the MEA of dominant males increases sensitivity to social stress (93).”

    From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [93]

  • In adult hamsters, dominant males have more androgen receptor expression in the medial amygdala (MEA) than subordinates.

    “In adult hamsters, dominant males have more androgen receptor expression in the medial amygdala (MEA) than subordinates, and pharmacological inhibition of AR in the MEA of dominant males increases sensitivity to social stress (93).”

    From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [93]

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Authors
Cooper, M. A., Clinard, C. T., Dulka, B. N., Grizzell, J. A., Loewen, A. L., Campbell, A. V., & Adler, S. G.
Affiliations
  • University of Tennessee at Knoxville (US)
  • Dalton State College (US)
  • University of Wisconsin–Milwaukee (US)
  • University of Colorado Boulder (US)
Corresponding author
Cooper, Matthew A.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2021-07
Volume
129
Pages
105249
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2021.105249
PMC
PMC8217359
OpenAlex
W3158832939
Cited by
23
References
6
Citations by year
2026: 3 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 2
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Foundation for the National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
androgen receptor, estrogen receptor alpha, medial amygdala, social dominance, social defeat stress, social avoidance, flutamide, testosterone, sex differences, golden hamster, stress vulnerability, plasma steroids
MeSH terms
Amygdala, Animals, Dominance-Subordination, Female, Cricetinae, Male, Receptors, Androgen, Gonadal Steroid Hormones, Stress, Psychological

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