Glutamate agonists activate the hypothalamic-pituitary-adrenal axis through hypothalamic paraventricular nucleus but not through vasopressinerg neurons

Brain Res. 2005 Jan 21;1031(2):185-93. doi: 10.1016/j.brainres.2004.10.034.


The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in the stress processes. The nucleus paraventricularis hypothalami (PVN) with corticotropin-releasing hormone (CRH)-containing and arginine vasopressin (AVP)-containing neurons is the main hypothalamic component of the HPA. The glutamate, a well-known excitatory neurotransmitter, can activate the HPA inducing adrenocorticotropin hormone (ACTH) elevation. The aim of our study was to examine the involvement of PVN and especially AVP in glutamate-induced HPA activation using agonists of the N-methyl-d-aspartate (NMDA) and kainate receptors. Two approaches were used: in male Wistar rats the PVN was lesioned, and AVP-deficient homozygous Brattleboro rats were also studied. Blood samples were taken through indwelling cannula and ACTH, and corticosterone (CS) levels were measured by radioimmunoassay. The i.v. administered NMDA (5 mg/kg) or kainate (2.5 mg/kg) elevated the ACTH and CS levels already at 5 min in control (sham-operated Wistar or heterozygous Brattleboro) rats. The PVN lesion had no influence on basal ACTH and CS secretion but blocked the NMDA- or kainate-induced ACTH and CS elevations. The lack of AVP in the Brattleboro animals had no significant influence on the basal or glutamate-agonists-induced ACTH and CS elevations. Our results suggest that NMDA and kainate may activate the HPA axis at central (PVN) level and not at the level of pituitary or adrenal gland and that AVP has minor role in glutamate-HPA axis interaction. The time course of the ACTH secretion was different with NMDA or kainate. If we compared the two curves, the results were not coherent with the general view that NMDA activation requires previous kainate activation. Although it has to be mentioned that the conclusion which can be drawn is limited, the bioavailability of the compounds could be different as well.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / metabolism*
  • Analysis of Variance
  • Animals
  • Arginine Vasopressin / deficiency
  • Arginine Vasopressin / physiology*
  • Corticosterone / metabolism*
  • Excitatory Amino Acid Agonists / administration & dosage
  • Glutamic Acid / physiology
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology*
  • Injections, Intravenous
  • Kainic Acid / administration & dosage
  • Male
  • N-Methylaspartate / administration & dosage
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / physiology*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology*
  • Rats
  • Rats, Brattleboro
  • Rats, Wistar
  • Species Specificity


  • Excitatory Amino Acid Agonists
  • Arginine Vasopressin
  • Glutamic Acid
  • N-Methylaspartate
  • Adrenocorticotropic Hormone
  • Kainic Acid
  • Corticosterone