Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus

Physiol Behav. 2003 Mar;78(3):365-73. doi: 10.1016/s0031-9384(03)00014-3.


A gradual decrement in hypothalamic-pituitary-adrenal (HPA) activity is observed following repeated exposure to the same stressor, such as repeated restraint. This decrement, termed habituation, may be partly due to alterations in corticosterone-mediated negative feedback inhibition of the HPA axis. We have previously found that the posterior division of the paraventricular thalamus (pPVTh) regulates habituated HPA activity without altering HPA responses to acute stress. Therefore, in the present study, we examined the role of the pPVTh in delayed feedback inhibition of plasma corticosterone responses to repeated restraint. Dexamethasone was administered subcutaneously 2 h prior to 30 min restraint to induce delayed negative feedback inhibition of the HPA axis. In the first experiment, we determined that a 0.05-mg/kg dose of dexamethasone produced submaximal suppression of corticosterone responses to acute restraint and used this dose in the remainder of the experiments. In Experiment 2, we examined dexamethasone-induced feedback inhibition to corticosterone responses to a single or eighth restraint exposure since negative feedback functions in chronically stressed rats are not well studied. We found that corticosterone levels following dexamethasone treatment were similar in repeatedly restrained compared to acutely restrained rats. In Experiment 3, we lesioned the pPVTh and examined dexamethasone-induced feedback inhibition of corticosterone responses to a single or eighth exposure to restraint. pPVTh lesions attenuated dexamethasone-induced inhibition of corticosterone at 30 min in chronically stressed rats but had no effect in acutely stressed rats. These data suggest that negative feedback functions are maintained in rats exposed to repeated restraint and implicate the pPVTh as a site that contributes to these negative feedback functions specifically under chronic stress conditions.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Corticosterone / blood
  • Corticosterone / metabolism
  • Dexamethasone / pharmacology
  • Feedback, Physiological / drug effects
  • Feedback, Physiological / physiology*
  • Glucocorticoids / pharmacology
  • Habituation, Psychophysiologic / drug effects
  • Habituation, Psychophysiologic / physiology*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Midline Thalamic Nuclei / drug effects
  • Midline Thalamic Nuclei / physiology
  • Midline Thalamic Nuclei / physiopathology*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Stress, Physiological / metabolism*
  • Stress, Psychological / metabolism
  • Time


  • Glucocorticoids
  • Dexamethasone
  • Corticosterone