Effects of Estradiol on Post-Traumatic Stress Disorder Symptoms
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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Post-traumatic stress disorder PTSD is a complex anxiety-related disorder that is caused by a traumatic or life-threatening event. This disorder is defined by a triad of clustered symptomatology including re-experiencing through intrusive thoughts and dreams persistent avoidance of stimuli associated with the trauma along with numbing of general responsiveness and hyperarousal not present before the event. Current treatments are beneficial to some patients but many continue to suffer from this debilitating disease and no preventative treatments are available. The underlying biological mechanism leading to PTSD is still elusive thus, the present research evaluates a potentially useful chronic stress paradigm in a rat model to mimic PTSD symptomatology. Additionally, the efficacy of estrogen receptor ER agonists as a preventative treatment for PTSD symptomatology was examined. Adult ovariectomized Sprague-Dawley rats were treated with vehicle VEH, 17Beta-estradiol E2, propylpyrazoletriol PPTER-alpha agonist, or diarylpropionitrile DPNERBeta agonist. Half the animals from each treatment were immobilized 60 minday for 22 days. These rats also had attenuated corticosterone levels, suggesting that the hypothalamic-pituitary-adrenal axis HPA response to stress was altered. Behavioral measures show stressed animals had exaggerated startle responses and an increase in tolerance to thermal pain. In response to hormone treatment, rats administered E2, PPT and DPN had attenuated exaggerated startle response. Furthermore, E2 and PPT were anxiolytic while E2, PPT, and DPN treatment improved the animals latency to escape from an anxious environment. In summary, the results of this study show that chronic immobilization stress disrupts the HPA axis and exaggerates certain behaviors reminiscent of PTSD in humans. Treatment with E2 or its agonists counteract some of the negative effects of chronic immobilization stress in the female rat.
- Medicine and Medical Research