Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of the amygdala impair HPA axis responsiveness and regulation in infant rhesus macaques (Macaca mulatta)?

Brain Res. 2006 Feb 3;1071(1):97-104. doi: 10.1016/j.brainres.2005.11.027. Epub 2006 Jan 17.


In response to stressful events, the HPA axis is activated triggering the successive release of CRF, ACTH, and glucocorticoids. The glucocorticoids in turn provide a negative feedback signal to terminate the stress response. The amygdala and the hippocampus are involved in the regulation of the HPA axis. In rodents, their respective roles have been identified; the amygdala exerts a stimulatory effect, whereas the hippocampus provides negative feedback control. In primates, however, their regulatory roles are still not well defined. The present study compared HPA axis responsiveness and regulation in 3- to 5-month-old rhesus macaques that received neonatal (15 +/- 3 days old) bilateral ibotenic acid lesions of the hippocampus or amygdala, or sham lesions. Group differences in plasma cortisol response to separation from the mother and relocation in a novel environment were assessed as well as response to dexamethasone suppression and ACTH challenge. Results revealed that the initial cortisol levels after separation/relocation did not differ between groups. Subjects with hippocampus lesions did not show a suppression of cortisol in response to dexamethasone, suggesting a loss of negative feedback control of HPA regulation. Subjects with amygdala and sham lesions did not differ in response to dexamethasone. Indeed, bilateral neonatal lesions of the amygdala have little impact on HPA axis responsiveness and regulation in contrast to lesions in adult monkeys. Finally, females displayed higher cortisol levels than males, independently of their lesion, indicating that the development of sex differences in the regulation of the HPA axis does not involve the amygdala or hippocampus.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenocorticotropic Hormone / administration & dosage
  • Amygdala / injuries
  • Amygdala / pathology
  • Amygdala / physiology*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Dexamethasone / administration & dosage
  • Excitatory Amino Acid Agonists / toxicity*
  • Female
  • Hippocampus / injuries
  • Hippocampus / pathology
  • Hippocampus / physiology*
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology*
  • Ibotenic Acid / toxicity*
  • Macaca mulatta
  • Magnetic Resonance Imaging / methods
  • Male
  • Maternal Deprivation
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology*


  • Excitatory Amino Acid Agonists
  • Ibotenic Acid
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Hydrocortisone