Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist

Am J Physiol. 1999 May;276(5):R1461-8. doi: 10.1152/ajpregu.1999.276.5.R1461.


We previously reported that rats exposed to repeated restraint (3 h/day for 3 days) experience temporary hypophagia and a sustained reduction in body weight compared with nonrestrained controls. Studies described here determined the involvement of central corticotropin-releasing factor (CRF) receptors in the initiation of this chronic response to acute stress. In experiment 1, Sprague-Dawley rats were fitted with cannulas in the lateral ventricle and infused with 50 micrograms of alphahCRF-(9-41) or saline immediately before restraint on each of the 3 days of restraint. The receptor antagonist inhibited hypophagia and weight loss on day 1 of restraint but not on days 2 and 3. In experiment 2, 10 micrograms of alphahCRF-(9-41) or saline were infused into the third ventricle immediately before each restraint. The receptor antagonist totally blocked stress-induced hypophagia and weight loss. These results demonstrate that CRF receptors located in or near the hypothalamus mediate the acute responses to stress that lead to a permanent change in the hormonal or metabolic processes that determine body weight and body composition.

Publication types

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

MeSH terms

  • Animals
  • Body Composition
  • Brain Chemistry / physiology
  • Cerebral Ventricles / chemistry*
  • Cerebral Ventricles / physiology
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / pharmacology*
  • Eating / drug effects
  • Injections, Intraventricular
  • Male
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Restraint, Physical
  • Stress, Physiological / physiopathology*
  • Weight Loss / drug effects*


  • Peptide Fragments
  • Receptors, Corticotropin-Releasing Hormone
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)
  • Corticosterone