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"UNDERSTANDING CHANGES IN AROUSAL, STRESS REACTIVITY AND COPING AFTER MILD TRAUMATIC BRAIN INJURY IN RATS: IMPLICATIONS FOR ANXIETY VULNERABILITY"

by
Pelin Avcu
Integrative Neurosciences Program
B.A. 2009, Bosphorus University, Istanbul - Turkey



Thesis Advisor: Richard J. Servatius, Ph.D.
Professor
Department of Neurology & Neurosciences

Friday, May 29, 2015
12:00 p.m., Pharm Phys Conference Room


Abstract

Mild traumatic brain injury (mTBI) has been associated with post-traumatic stress disorder (PTSD) among United States military service members involved in recent conflicts in Iraq and Afghanistan. In the military, concussions often occur in a highly traumatic context, which makes it difficult to determine whether post-injury development of PTSD is a result of psychological features of the traumatic event or a primary outcome of mTBI induced neurochemical dysfunction. PTSD is conceptualized as an interaction of individual vulnerabilities (e.g., being female, behaviorally inhibited temperament) and traumatic experiences to induce sequelae conforming to heightened arousal, avoidance and re-experiencing. In the present thesis work, a diathesis-stress approach is employed to investigate whether mTBI further enhances the development of PTSD symptoms (hyperarousal and avoidance) in behaviorally inhibited temperament and female rats. Contrary to our predictions, arousal assessed through acoustic startle reflex (ASR) paradigm was found to be persistently attenuated in behaviorally inhibited Wistar Kyoto (WKY) rats after mTBI; and stress reactivity (indexed by basal and stress levels of plasma corticosterone) was unaffected. Moreover, a separate study showed that mTBI produces a fairly selective sex specific deficit in effectively coping with predictable stressors (avoidance) in male mTBI rats. Sex specific impairment in avoidance learning is not accountable through sex differences in the degree of injury induced dysfunction (ASR attenuation is similar), inability to predict future aversive events (associative learning is unaffected), and to instrumentally control stress exposure (efficient escape responding). These neurobehavioral and physiological patterns observed after mTBI are inconsistent with PTSD sequela, and more conducive to an interpretation of depression. Reduced expression of avoidance that is not secondary to motor or associative learning impairment has been associated with depression in animal models. The impairment of active avoidance in male rats has the promise to be a new neurobehavioral marker for mTBI with its direct implications for mental health.


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