An ACTH/MSH(4-9) analog counteracts the behavioral effects of a mineralocorticoid receptor antagonist.
The ACTH/MSH(4-9) analog Org2766 has been demonstrated to counteract age-related behavioral and morphological parameters especially those related to hippocampal functioning. Hippocampal mineralocorticoid receptors (MRs) are known to decline in the senescent rat. This decrease can be also counteracted by a chronic treatment with an ACTH(4-9) analog. The apparent effect of the peptide on hippocampal functioning prompted us to study a possible interaction between ACTH and MRs at a behavioral level. A chronic treatment with the ACTH(4-9) analog prevented the behavioral alteration induced by a specific MR antagonist (RU28318; 100 ng/microliters, ICV) in the Morris water maze and a step-through avoidance task. A possible role for neuronal excitation, involving MR activation, in peptide-facilitated behavioral recovery as seen in lesion studies and aging is discussed.
Center of Bio-Pharmaceutical Sciences, Division of Medical Pharmacology, University of Leiden, The Netherlands.
M S
MS
Oitzl
M
M
Josephy
B M
BM
Spruijt
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D008297:Male; D008901:Mineralocorticoids; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013037:Spatial Behavior; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D008901:Mineralocorticoids; D010446:Peptide Fragments; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013148:Spironolactone; C013765:Org 2766; C041006:RU 28318; D000324:Adrenocorticotropic Hormone