Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat

Neuroendocrinology. 1989 Nov;50(5):597-604. doi: 10.1159/000125287.


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)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / metabolism*
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Corticosterone / metabolism
  • Corticosterone / pharmacology
  • Dexamethasone / pharmacology
  • Down-Regulation / drug effects
  • Feedback* / physiology
  • Handling, Psychological*
  • Hippocampus / metabolism*
  • Rats
  • Receptors, Glucocorticoid / metabolism*
  • Stress, Physiological / physiopathology*


  • Receptors, Glucocorticoid
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Corticosterone