FACILITATION OF FEEDBACK INHIBITION THROUGH BLOCKADE OF GLUCOCORTICOID RECEPTORS IN THE HIPPOCAMPUS

In the present study the effects of intracerebroventricular (icv) and intrahippocampal administration of corticosteroid antagonists on basal hypothalamic-pituitary-adrenal (HPA) activity around the diurnal peak were compared in male Wistar rats. In two separate experiments the gl ucocorticoid receptor (GR) antagonist RU 38486 and the mineralocortico id receptor (MR) antagonist RU 28318 were tested. One hour after GR an tagonist injection, significant increases in plasma ACTH and corticost erone levels were observed in the icy treated rats, when compared to v ehicle. In contrast, a significant decrease in ACTH levels, and a slig ht, but non-significant decrease in corticosterone concentrations were attained one hour after intrahippocampal injection of the GR antagoni st. Injection of the MR antagonist, on the other hand, resulted in enh anced ACTH and corticosterone levels irrespective of the site of injec tion. These findings suggest that negative feedback inhibition at the circadian peak involves hippocampal MRs and extrahippocampal (hypothal amic) GRs. The latter feedback inhibition overrides a positive feedbac k influence exerted by endogenous corticosteroids through hippocampal GRs.