Glucocorticoid receptor antagonists in the hippocampus modify the negative feedback following neural stimuli.

The effects of local glucocorticoid receptor antagonists implanted into the dorsal hippocampus on the hypothalamo-pituitary-adrenal (HPA) axis responses following neural stimuli in freely moving rats, as well as their effects on the negative feedback exerted by dexamethasone (DEX) was studied in male rats. In animals with hippocampal cholesterol implants, photic and acoustic stimuli caused depletion in median eminence (ME) CRH-41 and a consequent rise in plasma ACTH and corticosterone levels. These effects were inhibited by systemic DEX, and the latter phenomenon was partially reversed by hippocampal implants of glucocorticoid (GR) and to a lesser degree by mineralocorticoid (MR) receptor antagonists. These data indicate that GR and MR receptors in the hippocampus play a role in the glucocorticoid negative feedback on the HPA axis, although the hippocampus may have also a modulatory effect, which does not depend on glucocorticoids.