UCLA

Exposure to traumatic stress results in a number of physiological and psychological changes that interrupt attempts at active coping with further stress. These changes can lead to disorders such as Post-traumatic Stress Disorder (PTSD) and major depression. The learned helplessness model has long been used to model PTSD and comorbid depression following trauma in animals. Rats given traumatic stress show exaggerated fear responding and escape deficits following re-exposure to a relatively mild stressor 24 hours later. We have hypothesized that they transition during test from an anxious, agitated state to one of conservation-withdrawal, characterized by sensory unresponsiveness, cognitive dullness, and behavioral depression. This dissertation focuses on two methods of building resilience to trauma in the learned helplessness procedure, as well as elucidates a potential mechanism of action of the conservation-withdrawal state normally observed following trauma. Chapter One utilizes the concept of hormesis as a resilience-building technique. Hormesis is the process by which small stresses build resilience to large stresses. Rats were exposed to a number of parameters of hormetic stress in an effort to prevent the exaggerated fear conditioning and shuttle-escape deficits normally observed following traumatic stress. We examined stressor severity, pattern of rest, and number of pre-exposure stressors to define the most effective hormetic procedures at eliminating PTSD-like symptoms. Chapter Two examines a second method of building stress resilience – post-stress glucose consumption. Rats received 18hr access to a glucose cocktail immediately following stress exposure. We found that post-stress glucose is a simple and effective method to prevent the deleterious effects that normally occur following trauma. Glucose eliminated the shift to conservation-withdrawal during shuttle-box testing, facilitated hormetic stress training, and built resilience to multiple traumas. Lastly, Chapter Three discusses striatal adenosine signaling as a potential mechanism of action of glucose in preventing the transition to conservation-withdrawal during test. We discovered that blocking adenosine A2A receptor activation in the core and shell of the nucleus accumbens before test eliminates conservation-withdrawal. Overall, the evidence suggests that the metabolic reaction to stress is essential to related pathology.