PERMANENT UP-REGULATION OF HIPPOCAMPAL MINERALOCORTICOID RECEPTORS AFTER NEONATAL ADMINISTRATION OF ACTH-(4-9) ANALOG ORG-2766 IN RATS

The development of brain corticosteroid receptors may be permanently m odified by perinatal hormone treatments, in particular by hormones of the hypothalamic-pituitary-adrenal axis. Changes in binding characteri stics of corticosteroid receptors were investigated in rats treated su bcutaneously with 1 mu g/g body wt of the ACTH-(4-9) analog peptide OR G 2766 once daily at postnatal days 1, 3 and 5. [H-3]Corticosterone (C ORT) binding capacity (B-max) and affinity (K-d) mere determined at 1- , 2- and 3-weeks old and adult ages in the hippocampal cytosol by usin g saturation analysis. Mineralocorticoid type receptor (MR) and glucoc orticoid receptor (GR) sites were measured separately with single-poin t analysis applying a selective glucocorticoid ligand RU 28362 saturat ing GR. An increase in [3H]CORT binding capacity was found during post natal development which remained permanently high up to adult age. Sep arate analysis of MR and GR expression indicated that the increment in the number of corticoid receptor sites was due to an increase in numb er of MRs in both the young and adult rats. Ie was concluded that neon atal injections of ACTH-(4-9) peptide resulted in a permanent and sele ctive upregulation of hippocampal MRs, which may underlie the previous ly observed increased vigilance and novelty-induced behavioral reactiv ity of the peptide-treated adult rats (Felszeghy, K., Sasvari, M. and Nyakas, C., Horm. Behav., 27 (1993) 380-396). (C) 1997 Elsevier Scienc e B.V.