Post-traumatic stress disorder (PTSD) develops after exposure to trauma and is associated with dysfunction in the normal stress response. Women are twice as likely as men to develop PTSD and tend to experience different symptoms and comorbidities than men, but the neurobiological basis for these pervasive sex differences is poorly understood due to the overwhelming male bias in the preclinical research. My dissertation work tested the novel hypothesis that the neurobiological mechanisms underlying the traumatic stress response in male and female rats are fundamentally different and may be related to normal sex differences in circulating levels of adult gonadal hormones. These experiments are the first to compare adult male and female rats across two rodent models of PTSD, single prolonged stress and predator exposure. I report a highly sex-specific traumatic stress response that recapitulates fundamental differences of PTSD in men and women. Surprisingly, these sex differences were largely independent of adult circulating gonadal hormones, housing conditions, and types of stress. Two standard measures, the acoustic startle response and dexamethasone suppression test to measure the negative feedback control of the stress hormone response, suggest that female rats, unlike male rats, are resilient to the effects of traumatic stress. However, other measures like sucrose preference and social interaction make it clear that females are not resilient, but simply respond differently to trauma than males. Dramatic sex differences in how trauma affects cFos activation and glucocorticoid receptor expression in the brain lend further support to the idea that the trauma response of males and females is fundamentally different, and likely determined prior to adulthood. Factors that mediate differences in how individuals adjust after trauma are attractive targets for the prevention and treatment of PTSD, and identifying such factors of resilience depends on understanding the various ways the traumatic stress response manifests in different individuals. I propose that sex differences offer a promising inroad for addressing this issue.
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