Effects of defeat stress on behavioral flexibility in males and females: modulation by the mu‐opioid receptor
Open accessAbstract
Behavioral flexibility is a component of executive functioning that allows individuals to adapt to changing environmental conditions. Independent lines of research indicate that the mu opioid receptor (MOR) is an important mediator of behavioral flexibility and responses to psychosocial stress. The current study bridges these two lines of research and tests the extent to which social defeat and MOR affect behavioral flexibility and whether sex moderates these effects in California mice (Peromyscus californicus). Males and females assigned to social defeat or control conditions were tested in a Barnes maze. In males, defeat impaired behavioral flexibility but not acquisition. Female performance was unaffected by defeat.MOR binding in defeated and control mice in the orbitofrontal cortex (OFC), striatum and hippocampus was examined via autoradiography. Stressed males had reduced MOR binding in the OFC whereas females were unaffected. The MOR antagonist beta‐funaltrexamine (1 mg/kg) impaired performance in males naïve to defeat during the reversal phase but had no effect on females. Finally, we examined the effects of the MOR agonist morphine (2.5 and 5 mg/kg) on stressed mice. As expected, morphine improved behavioral flexibility in stressed males. The stress‐induced deficits in behavioral flexibility in males are consistent with a proactive coping strategy, including previous observations that stressed male California mice exhibit strong social approach and aggression. Our pharmacological data suggest that a down‐regulation of MOR signaling in males may contribute to sex differences in behavioral flexibility following stress. This is discussed in the framework of coping strategies for individuals with mood disorders.
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Social defeat induces deficits in reversal learning in male but not female California mice.
“Social defeat induces deficits in reversal learning in male but not female California mice (102)”
From Sexual differentiation of neural mechanisms of stress sensitivity during puberty (2023) · cites this paper as [102]
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- Authors
- Laredo, S. A., Steinman, M. Q., Robles, C. F., Ferrer, E., Ragen, B. J., & Trainor, B. C.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Laredo, Sarah A.
- Trainor, Brian C.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2015-01-23
- Volume
- 41
- Issue
- 4
- Pages
- 434-441
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC4331223
- OpenAlex
- W2000694307
- Cited by
- 75
- References
- 12
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 15 · 2017: 5 · 2016: 9 · 2015: 3 · 2014: 1
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (GRF)
- National Institutes of Health (F31 MH095253-01, R01 MH085069)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- social defeat stress, behavioral flexibility, mu-opioid receptor, sex differences, California mouse, Peromyscus californicus, orbitofrontal cortex, beta-funaltrexamine, morphine, proactive coping, executive function, mood disorders
- MeSH terms
- Aggression, Animals, Female, Frontal Lobe, Hippocampus, Male, Peromyscus, Sex Factors, Stress, Psychological, Receptors, Opioid, mu, Maze Learning
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