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Biol Psychiatry. 2016 Sep 1;80(5):406-14. doi: 10.1016/j.biopsych.2015.10.007. Epub 2015 Oct 19.

Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

Author information

1
Molecular, Cellular, Integrative Physiology Graduate Group, University of California, Davis, Davis, California; Department of Psychology, University of California, Davis, Davis, California.
2
Department of Psychology, University of California, Davis, Davis, California; Animal Behavior Graduate Group (ND-W, SAL, BCT), University of California, Davis, Davis, California.
3
Department of Psychology, University of California, Davis, Davis, California; Neuroscience Graduate Group, University of California, Davis, Davis, California.
4
Department of Psychology, University of California, Davis, Davis, California.
5
Department of Psychology, University of California, Davis, Davis, California; Neuroscience Graduate Group, University of California, Davis, Davis, California. Electronic address: bctrainor@ucdavis.edu.

Abstract

BACKGROUND:

Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice.

METHODS:

We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14).

RESULTS:

Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test.

CONCLUSIONS:

Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress.

KEYWORDS:

Anxiety; Bed nucleus of the stria terminalis; Mood disorders; Oxytocin; Paraventricular nucleus; Peromyscus; Posttraumatic stress disorder; Sex differences; Social behavior

PMID:
26620251
PMCID:
PMC4837091
DOI:
10.1016/j.biopsych.2015.10.007
[Indexed for MEDLINE]
Free PMC Article

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