Adult rats handled (H) daily for the first 3 weeks of life show a dramatically altered adrenocortical response to stress. We found that H animals secreted less ACTH and corticosterone (B) during and following the termination of stress than did nonhandled (NH) controls. In contrast, H and NH animals did not differ in basal B secretion at any point in the diurnal cycle, nor in adrenocortical responses to exogenously administered oCRF or ACTH. Moreover, the clearance rate for B was similar in H and NH animals. H animals were more sensitive than NH animals to the inhibitory effects of either B or dexamethasone on stress-induced adrenocortical activity. In a dose-response study, both glucocorticoids administered 3 h prior to testing suppressed the adrenocortical response to a 20-min restraint stress to a greater extent in the H animals. Handling increased type II, glucocorticoid receptor binding capacity in the hippocampus of adult animals (∼50% increase in capacity, with no change in affinity). There were no handling-induced changes in type II receptor binding capacity in the hypothalamus or pituitary, nor in type I receptor binding capacity in the hippocampus. Following chronic (5 mg/kg/day) treatment with B, hippocampal type II receptor binding capacity was significantly reduced in the B-treated H animals, compared with saline-treated H animals, and indistinguishable from saline-treated NH animals. Down-regulated H animals, like NH animals, hypersecreted B following the termination of stress in comparison to the saline-treated H animals. These data suggest that the increase in hippocampal type II glucocorticoid receptors is a critical feature for the handling effect on the adrenocortical stress response. The increase in receptors appears to render the H animals more sensitive to the negative feedback effects of the high levels of circulating glucocorticoids, exerting a greater inhibitory control over subsequent adrenocortical activity.
Michael J. Meaney, Douglas Hospital Research Centre, 6875 Boulevard LaSalle, Montreal, Que. H4H 1R3 (Canada)
Received: October 31, 1988
Accepted after revision: April 28, 1989
Published online: April 02, 2008
Number of Print Pages : 8
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 50, No. 5, Year 1989 (Cover Date: 1989)
Journal Editor: Millar R.P. (Edinburgh)
ISSN: 0028–3835 (Print), eISSN: 1423–0194 (Online)
For additional information: http://www.karger.com/NEN
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