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.

[1]  Willem Hendrik Gispen,et al.  Org2766 improves performance of rats with unilateral lesions in the fimbria fornix in a spatial learning task , 1990, Brain Research.

[2]  W. Gispen,et al.  On the neurotrophic action of melanocortins. , 1987, Progress in brain research.

[3]  P. Bo,et al.  Centrally administered N-terminal fragments of ACTH (1–10, 4–10, 4–9) display convulsant properties in rabbits , 1983, Peptides.

[4]  B. Spruijt,et al.  The MSH/ACTH(4–9) analog Org2766 counteracts isolation-induced enhanced social behavior via the amygdala , 1992, Peptides.

[5]  Philip W. Landfield,et al.  Hippocampal neurobiological mechanisms of age-related memory dysfunction , 1988, Neurobiology of Aging.

[6]  Berry M. Spruijt,et al.  Approach, avoidance, and contact behavior of individually recognized animals automatically quantified with an imaging technique , 1992, Physiology & Behavior.

[7]  M. Joëls,et al.  Control of neuronal excitability by corticosteroid hormones , 1992, Trends in Neurosciences.

[8]  E. R. Kloet,et al.  Neurotrophic ACTH analogue promotes plasticity of type I corticosteroid receptor in brain of senescent male rats , 1988, Neurobiology of Aging.

[9]  E. R. Kloet,et al.  Spatial learning and the hippocampal corticosterone receptor system of old rats: effect of the ACTH4–9 analogue ORG 2766 , 1984, Brain Research.

[10]  E. D. Kloet,et al.  The effect of aging on stress responsiveness and central corticosteroid receptors in the Brown Norway rat , 1992, Neurobiology of Aging.

[11]  A. Ratka,et al.  On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation. , 1989, Neuroendocrinology.

[12]  R. Ader,et al.  Retention of a passive avoidance response as a function of the intensity and duration of electric shock , 1972 .

[13]  B. Spruijt,et al.  The ACTH/MSH(4–9) analog Org2766 improves retrieval of information after a fimbria fornix transection , 1990, Peptides.

[14]  M. Oitzl,et al.  Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. , 1992, Behavioral neuroscience.

[15]  J. Born,et al.  ACTH and attention in humans: a review. , 1986, Neuropsychobiology.

[16]  B. Spruijt.  Effects of the ACTH4–9 analog Org2766 on brain plasticity: Modulation of excitatory neurotransmission? , 1992, Psychoneuroendocrinology.

[17]  V. Chan‐Palay,et al.  The Hippocampus : new vistas , 1989 .

[18]  B. Spruijt.  An ACTH4–9 analog enhances social attention in aging rats: A longitudinal study , 1992, Neurobiology of Aging.

[19]  B. McEwen,et al.  The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. , 1986, Endocrine reviews.

[20]  P. Landfield,et al.  Modulation of brain aging correlates by long-term alterations of adrenal steroids and neurally-active peptides. , 1987, Progress in brain research.

[21]  W. Gispen,et al.  A simple technique for rapid implantation of a permanent cannula into the rat brain ventricular system. , 1979, Laboratory animal science.

[22]  F. Gage,et al.  Functional correlates of compensatory collateral sprouting by aminergic and cholinergic afferents in the hippocampal formation , 1983, Brain Research.

[23]  Fred H. Gage,et al.  Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents , 1983, Brain Research.

[24]  R. Sapolsky,et al.  Effect of neonatal handling on age-related impairments associated with the hippocampus. , 1988, Science.

[25]  E. D. Kloet,et al.  Brain corticosteroid receptor balance and homeostatic control , 1991 .