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Vol. 50, No. 5, 1989
Issue release date: 1989
Neuroendocrinology 1989;50:597–604
Original Paper

Neonatal Handling Alters Adrenocortical Negative Feedback Sensitivity and Hippocampal Type II Glucocorticoid Receptor Binding in the Rat

Meaney M.J. · Aitken D.H. · Viau V. · Sharma S. · Sarrieau A.
Douglas Hospital Research Centre, Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada


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.

 goto top of outline Author Contacts

Michael J. Meaney, Douglas Hospital Research Centre, 6875 Boulevard LaSalle, Montreal, Que. H4H 1R3 (Canada)

 goto top of outline Article Information

Received: October 31, 1988
Accepted after revision: April 28, 1989
Published online: April 02, 2008
Number of Print Pages : 8

 goto top of outline Publication Details

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)

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