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Clinical research suggests that a blunted corticosteroid response to trauma may be associated with increased risk of developing post-traumatic stress disorder (PTSD). Therefore, we examined the influence of a blunted corticosterone response to stress on the development of PTSD-like behaviors, such as increased anxiety and impaired learning and memory, in rats. Male Sprague-Dawley rats were injected with metyrapone, an inhibitor of corticosterone synthesis, or vehicle prior to being exposed to an adult female cat for one hour. One week later, the rats were tested for anxiety-like behaviors (e.g., reduced open arm exploration, decreased locomotor activity) on an elevated plus maze and for spatial learning and memory in the radial-arm water maze. Analyses of post-stress serum samples verified that metyrapone blocked the stressinduced increase of corticosterone levels. Behaviorally, the blunted corticosterone response to stress had no effect on the development of anxiety-like behaviors. On the other hand, we found that metyrapone administration prior to stress significantly impaired long-term spatial memory. These findings suggest that reduced corticosteroid levels could interact with stress to produce deleterious effects on cognitive performance. Moreover, because anxiety-like behaviors were not intensified by the blunted corticosteroid response to stress, our findings also suggest that specific physiological responses to an acute trauma may intensify some, but not all, PTSD-like symptoms.

Blunted Corticosterone Response to Acute Predator Stress Results in Long-Term Spatial Memory Impairment