EFFECTS OF THE ANTIGLUCOCORTICOID RU-38486 ON THE INDUCTION OF LEARNED HELPLESS BEHAVIOR IN SPRAGUE-DAWLEY RATS

Learned helplessness (LH) is induced by exposure to an inescapable or uncontrollable stressor which results in an inability to escape or avo id the same stressor when subsequently presented in a different contex t. In order to understand which central mechanisms may influence the e xpression of the learned helpless phenotype, we have pursued an experi mental approach that seeks to elucidate the behavioral effects of gluc ocorticoid (GC) hormones in this animal model of depression. We have p reviously shown that the induction of LH behavior is enhanced by adren alectomy, an effect that is reversed by corticosterone. In this study, our aim was to attempt to locate CNS sites responsible for the observ ed effects of glucocorticoids on learned helpless behavior by introduc ing the type II GC receptor antagonist, RU 38486 to discrete brain reg ions. We did not observe a significant effect in LH with acute systemi c, acute dentate gyrus or intracerebroventricular injection of RU 3848 6 in contrast to previous studies using the Porsolt swim test, another animal model of depression. However, we were able to observe a signif icant change upon chronic administration to the dentate gyrus. These f indings suggest that glucocorticoids exert a long-term influence on st ress-induced behavior, presumably by affecting glucocorticoid responsi ve genes in the dentate gyrus.