Date of Award

5-10-2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

H. Elliott Albers

Second Advisor

Kim Huhman

Third Advisor

Geert de Vries

Fourth Advisor

Mark Wilson

Fifth Advisor

Craig Ferris

Abstract

There are profound sex differences in the incidence of many psychiatric disorders. While these disorders are frequently linked to social stress, little is known about sex differences in the underlying neural mechanisms. Individuals characterized by aggression and dominance are more resistant to social stress, whereas individuals characterized by docility and subordinace are more susceptible to social stress. The goal of this dissertation is to characterize sex differences in neural mechanisms that underlie aggression, dominance, and resistance to social stress. First, we explored sex differences in how serotonin (5-HT) and arginine vasopressin (AVP) regulate aggression and acquisition of dominance in Syrian hamsters. We tested the hypothesis that 5-HT in females and AVP in males facilitates aggression and acquisition of dominance. In females, 5-HT facilitates aggression and is associated with acquisition of dominance, whereas 5-HT reduces aggression in males. AVP, on the other hand, facilitates aggression and is associated with acquisition of dominance in males, whereas AVP reduces aggression in females. Next, we explored the same 5-HT and AVP systems in the context of social stress. First, we paired hamsters in stable, 14-day dominant/subordinate relationships and subsequently measured activation of 5-HT and AVP-containing neurons after social defeat. We hypothesized that dominance is associated with activation of 5-HT-containing neurons in females and AVP-containing neurons in males after social defeat. Socially defeated dominant females had higher 5-HT neuron activation than subordinate or control females, whereas socially defeated dominant males had lower AVP neuron activation than control males. In another set of experiments, we pharmacologically manipulated the 5-HT and AVP systems and observed subsequent resistance to social stress. Systemic injection of the selective serotonin reuptake inhibitor, fluoxetine, in males increased social avoidance after social defeat stress whereas fluoxetine had not effect on social avoidance in females. Microinjection of AVP into the anterior hypothalamus (AH) of female after social defeat decreased social avoidance. Microinjection of a 5-HT1a receptor agonist into the AH of male after social defeat decreased social avoidance. Taken together, these data show that there are sex differences in how 5-HT and AVP regulate aggression, dominance, and resistance to social stress in Syrian hamsters.

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