Corticosterone Administration to Promote Fear Memory Forgetting Process in an Animal Model of PTSD

摘要

Activation of glucocorticoid receptor signaling and its subsequent alterations has been implicated in the pathophysiological fear response to stress and the pathogenesis of stress-associated psychiatric disorders such as posttraumatic stress disorder (PTSD). To further examine the association between alterations in central glucocorticoid receptor signaling and the occurrence of stress-induced psychiatric symptoms, the present study, utilizing a learned helplessness stress model in rats, examines whether glucocorticoid receptor signaling activation shortly before or after stress might prevent the occurrence of stress-induced physical and behavioral abnormalities such as exaggerated acoustic startle response (ASR) and reduced body weight gain. Rats subjected to restraint/tail shock for three days have been shown to develop a long-lasting elevated ASR and reduced body weight gain, compared to non- stressed control animals. In this study, the glucocorticoid receptor agonist, corticosterone (3 mg/kg), will be administered 30 min before or after exposure of the animals to the stress protocol. Acoustic startle response (ASR), plasma corticosterone levels and body weight will be measured on Day -1 (baseline readings) and on Days 7, 14 and 21 after completion of the stress protocol. The glucocorticoid antagonist RU 486 was administered to determine the specificity of therapeutic efficacy of corticosterone.