Dissertation

The Sex-Specific Effects of Neuropeptide Receptors in the Bed Nucleus of the Stria Terminalis on Social Behavior

Duque-Wilckens, Natalia

2017

Overview

The neuropeptides oxytocin (OT) and vasopressin (AVP) are key regulators of social and emotional behaviors. Accumulating evidence suggesting a role of OT, AVP, and their receptors in the pathophysiology of psychiatric disorders has sparked interest in these systems as therapeutic targets. Nonetheless, the specific neural circuits mediating context and sex specific behavioral effects of OT and AVP are not fully understood. Using the California mouse model of social defeat, we previously found that social defeat stress increases the reactivity of OT neurons in the medioventral bed nucleus of the stria terminalis (BNSTmv) and paraventricular nucleus in female but not male California mice. We also found that intranasal administration of OT has no effect on male social interaction, but reduces this behavior in females, mirroring the effect of social defeat stress. Here we conducted a series of experiments aimed at identifying receptor populations involved in sex specific effects of stress on social interaction behavior and specific sites of action. First we studied the effects of sex and social defeat stress on AVP receptor V1a (V1aR) binding in the forebrain. In females but not males, V1aR binding in the BNSTmv was negatively correlated to social interaction behavior. We hypothesized that activation of this receptor population was mediating stress-induced social deficits, but Infusions of V1aR antagonist in to the BNSTmv had anxiogenic effects in both males and females. Next, we studied the effects of systemic administration of an OT receptor antagonist (OTA) on social behavior in control and stressed males and females. We found that one dose of OTA reverses the effects of stress on female social behavior, but has the opposite effects in males. To identify potential sites of action, we used immediate early gene immunohistochemistry in mice that received intranasal OT or control infusions. We found that stress increases EGR-1 immunoreactivity in the dorsolateral nucleus accumbens core and anteromedial BNST in females but not males. Based on these results, we performed site-specific injections of OTA in stressed females. A single dose of OTA within the anteromedial BNST rapidly reversed stress-induced social avoidance in females. Together, these results support the hypothesis that stress-induced hyperactivity of OT neurons contributes to some stress-induced changes in female social behavior by activating OT receptors, and that OTR antagonists may have unappreciated therapeutic potential for stress-induced psychiatric disorders.

• Publisher: ProQuest Dissertations & Theses
• Subject: Behavioral Sciences / Molecular biology / Neurosciences
• ISBN: 9780355151381, 0355151383