Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist.
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.
Smagin
G N
GN
Departments of Neuroscience and Biostatistics, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
Howell
L A
LA
Redmann
S
S
Ryan
D H
DH
Harris
R B
RB
D000818:Animals; D001823:Body Composition; D001923:Brain Chemistry / Q000502:physiology; D002552:Cerebral Ventricles / Q000737:chemistry* / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*; D015431:Weight Loss / Q000187:drug effects*
D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D003345:Corticosterone