Abstract for presentation at 6th World Congress on Stress

While the surge of corticosteroid hormones after a single stressful event is generally considered to promote behavioral adaptation, less beneficial effects may result from exposure to repetitive stressors, especially when these are uncontrollable and unpredictive. We have studied the effect of exposure to 21 days of unpredictable stress, on hippocampal function in adult male rats. It was observed that in the CA1 region many functions are disturbed by chronic stress, even when the tissue is studied one day after the last stressor i.e. when the pituitary-adrenal axis activity is low. For instance, compared to the situation in handled control animals serotonin responses are small, calcium currents are large and induction of long-term potentiation is impaired. Under those conditions, long-term potentiation in the dentate gyrus was also suppressed, as was neurogenesis. Moreover, calcium currents, glutamate responses and single cell gene expression profiles in dentate cells -normally not much affected by a high dose of corticosterone- were largely altered if tissue was exposed to a high dose of corticosterone against a background of chronic stress. Many of the cellular effects of chronic stress in the two hippocampal areas could be prevented by treatment with a very high dose of the glucocorticoid receptor antagonist RU 38486 during the last 4 days of the stress protocol. Overall, hippocampal cells may become more excitable and more vulnerable after a period of unpredictable stress, through a glucocorticoid receptor dependent process.