Degree Granting Department
David Diamond, Ph.D.
Paula Bickford, Ph.D.
Edward Levine, Ph.D.
Kristen Salomon, Ph.D.
PTSD, glucocorticoids, metyrapone, AF-DX 116, yohimbine
People who endure horrific, life-threatening experiences are at risk for developing post-traumatic stress disorder (PTSD). However, only about 25% of all individuals who experience trauma develop PTSD. Recent research indicates that the presence of certain physiological conditions, such as reduced cortisol and parasympathetic inhibition, during trauma may increase one's susceptibility to developing PTSD. Thus, I attempted to develop a novel animal model of PTSD and test the hypothesis that reduced adrenal and parasympathetic activity during stress would exacerbate its long-term effects on behavior.
In Experiment One, adult male rats were exposed to two stress sessions, each involving one hour of immobilization plus cat exposure. Before each session, rats were injected with vehicle, metyrapone, AF-DX 116, or both drugs. The second session occurred 10 days after the first and served to model a traumatic flashback. Stressed rats endured unstable housing conditions throughout the experiment to add an element of daily anxiety. Three weeks after the second session, all rats underwent a battery of tests to examine the lasting effects of stress on physiology and behavior. The results indicated that stressed rats exhibited heightened anxiety on the elevated plus maze, an exaggerated startle response, and greater blood pressure, relative to controls. Moreover, metyrapone, when combined with stress, led to significant short- and long-term spatial memory impairments.
Experiment Two assessed the effects of the same stress paradigm on rats' sensitivity to yohimbine, an alpha-2 adrenergic receptor antagonist. Yohimbine induces flashbacks and panic attacks in patients with PTSD; thus, I hypothesized that stressed rats would react abnormally to this agent. Stressed and unstressed rats were administered vehicle or yohimbine (1 mg/kg) 30 min prior to behavioral testing. The results indicated that stressed rats were hyperresponsive to yohimbine, as evidenced by a greater suppression of rearing, greater avoidance of the center of the open field, and a greater suppression of activity on the elevated plus maze, relative to controls. Collectively, the findings of these studies indicate that uncontrollable and unpredictable psychological stress produces lasting changes in the physiology and behavior of rats that resemble symptoms commonly observed in people with PTSD.
Scholar Commons Citation
Zoladz, Phillip R., "Uncontrollable and Unpredictable Stress with a Reminder Experience Induces Long-Lasting Effects on Physiology and Behavior: A Novel Approach to Modeling Post-Traumatic Stress Disorder in Rats" (2006). Graduate Theses and Dissertations.