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

Clinical research suggests that a blunted corticosteroid response to trauma may be associated with increased risk of developing post-traumatic stress disorder (PTSD). In order to more directly test this hypothesis, we examined the influence of a blunted corticosterone response to stress on the development of PTSD-like behaviors in rats. One-month-old, male Sprague-Dawley rats were injected with metyrapone, an inhibitor or corticosterone synthesis, or vehicle prior to being exposed to an adult female cat for one hour. A week later, the rats were tested for anxiety-like behavior on an elevated plus maze (EPM) and for spatial learning and memory in the radial-arm water maze (RAWM). Analyses of post-stress serum samples verified that metyrapone effectively blocked the stress-induced increase of rat corticosterone levels. Behaviorally, we found that stress, independent of drug, led to an increase in some anxiety-like behaviors (e.g., overall movement, head dips) on the EPM. More importantly, we found that metyrapone administration prior to stress significantly impaired long-term spatial memory in the RAWM. These findings indicate that a blunted corticosteroid response to stress could exacerbate its effects on cognitive performance. Moreover, because anxiety-like behaviors on the EPM 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.