Date of Award

Spring 1-1-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology & Neuroscience

First Advisor

Serge Campeau

Second Advisor

Heidi Day

Third Advisor

Robert Spencer

Fourth Advisor

Joanna Arch

Fifth Advisor

Benjamin Greenwood

Abstract

Stress can be a causative or exacerbating factor for many physical and psychiatric disorders. Several stress-related mood and anxiety disorders are about twice as prevalent in women as in men, such as major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder. Dysfunction and/or dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis have been implicated in each one of these psychopathologies. Therefore understanding how sex can affect the biological function of the HPA axis may inform the mechanism behind a female's vulnerability or susceptibility to the maladaptive effects of stress. The studies presented in this dissertation investigate the nature of sex differences in the HPA axis, and how the effect of sex on HPA axis function differs in a stress-specific way in rats. Specific focus is placed on extra-hypothalamic stress responsive neurocircuitry, and these chapters provide evidence that when sex differences in acute stress-induced HPA axis hormone release are observed, parallel differences are observed in the activation of several key brain regions known to modulate HPA axis function. Conversely, when no effect of sex on HPA axis hormone release is observed in response to a stressor of a different modality, brain activation of stress responsive neurocircuitry is also comparable in the male and female brain. Furthermore, regardless of the effect of sex on acute stress-induced HPA axis activity, repeated presentations of the same stressor produced similar extent of adaptation (habituation) of HPA axis activity. These data suggest that responses of the HPA axis to relatively mild stressors, whether acutely or repeatedly presented, are not likely to produce maladaptive changes in the female brain that could explain vulnerability to certain stress-related mental illnesses in women. Further research is needed to understand what could produce maladaptive changes to stress specifically in women.

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