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

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• 作者：Michael Q. Steinman^a ; ^b ; Natalia Duque-Wilckens^b ; ^c ; Gian D. Greenberg^b ; ^d ; Rebecca Hao^b ; Katharine L. Campi^b ; Sarah A. Laredo^b ; ^c ; Abigail Laman-Maharg^b ; ^d ; Claire E. Manning^b ; Ian E. Doig^b ; Eduardo M. Lopez^b ; Keenan Walch^b ; Karen L. Bales^b ; Brian C. Trainor^b ; ^d ; ^{bctrainor@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Anxiety ; Bed nucleus of the stria terminalis ; Mood disorders ; Oxytocin ; Paraventricular nucleus ; Peromyscus ; Posttraumatic stress disorder ; Sex differences ; Social behavior
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：1 September 2016
• 年：2016
• 卷：80
• 期：5
• 页码：406-414
• 全文大小：3531 K

文摘

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.