Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat.
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 (approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Meaney
M J
MJ
Douglas Hospital Research Centre, Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada.
Aitken
D H
DH
Viau
V
V
Sharma
S
S
Sarrieau
A
A
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005246:Feedback / Q000502:physiology; D006234:Handling, Psychological; D006624:Hippocampus / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone