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Sex-dependent Regulation of Social Avoidance by Oxytocin Signaling in the Ventral Tegmental Area

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Journal Behav Brain Res
Date 2024 Jan 25
PMID 38272188
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Abstract

It has been hypothesized that oxytocin increases the salience of social stimuli, whether the valence is positive or negative, through its interactions with the ventral tegmental area (VTA). Indeed, oxytocin neurons project to the VTA and activate dopamine neurons that are necessary for social experiences with positive valence. Surprisingly, though, there has not been an investigation of the role of oxytocin in the VTA in mediating social experiences with negative valence (e.g., social stress). Given that there are sex differences in how oxytocin regulates the salience of positively-valenced social interactions, we hypothesized that oxytocin acting in the VTA also alters the salience of social stress in a sex-dependent manner. To test this, female and male Syrian hamsters were site-specifically infused with either saline, oxytocin (9 μM), or oxytocin receptor antagonist (90 μM) into the VTA. Subjects were then exposed to either no defeat or a single, 15 min defeat by one RA. The day following social defeat, subjects underwent a 5 min social avoidance test. There was an interaction between sex and drug treatment, such that the oxytocin antagonist increased social avoidance compared to saline treatment in socially stressed females, while oxytocin decreased social avoidance compared to saline treatment in socially stressed males. Contrary to expectations, these results suggest that oxytocin signaling generally acts to decrease social avoidance, regardless of sex. These sex differences in the efficacy of oxytocin and oxytocin receptor antagonists to alter negatively-valenced social stimuli, however, should be considered when guiding pharmacotherapies for disorders involving social deficits.

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References
1.
Song Z, Borland J, Larkin T, OMalley M, Elliott Albers H . Activation of oxytocin receptors, but not arginine-vasopressin V1a receptors, in the ventral tegmental area of male Syrian hamsters is essential for the reward-like properties of social interactions. Psychoneuroendocrinology. 2016; 74:164-172. PMC: 6417503. DOI: 10.1016/j.psyneuen.2016.09.001. View

2.
Duque-Wilckens N, Steinman M, Busnelli M, Chini B, Yokoyama S, Pham M . Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress-Induced Social Avoidance in Female California Mice. Biol Psychiatry. 2017; 83(3):203-213. PMC: 5743604. DOI: 10.1016/j.biopsych.2017.08.024. View

3.
Steinman M, Duque-Wilckens N, Trainor B . Complementary Neural Circuits for Divergent Effects of Oxytocin: Social Approach Versus Social Anxiety. Biol Psychiatry. 2018; 85(10):792-801. PMC: 6709863. DOI: 10.1016/j.biopsych.2018.10.008. View

4.
Solomon M, Karom M, Huhman K . Sex and estrous cycle differences in the display of conditioned defeat in Syrian hamsters. Horm Behav. 2007; 52(2):211-9. DOI: 10.1016/j.yhbeh.2007.04.007. View

5.
Klumpp H, Amir N . Examination of vigilance and disengagement of threat in social anxiety with a probe detection task. Anxiety Stress Coping. 2009; 22(3):283-96. PMC: 3712328. DOI: 10.1080/10615800802449602. View