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.