Submitted on March 17, 2008
Accepted on October 13, 2008
Antagonism of Specific Corticotropin Releasing Factor Receptor Subtypes Selectively Modifies Weight Loss in Restrained Rats
Christina Chotiwat1 and Ruth B.S. Harris2*
1 Foods and Nutrition, University of Georgia, 30602, Georgia, United States
2 Foods and Nutrition, University of Georgia, Athens, Georgia, United States
* To whom correspondence should be addressed. E-mail: harrisrb{at}uga.edu.
Rats exposed to 3 hours of restraint stress on each of 3 days (RRS) lose weight on the days of RRS and gain weight at the same rate as controls after stress ends, but do not return to the weight of controls. RRS rats also show an exaggerated endocrine response to subsequent novel stressors. Studies described here tested the effects of corticotropin-releasing factor receptor (CRFR) antagonism on RRS-induced weight loss, hypophagia and corticosterone release during mild stress in the post-restraint period. Weight loss was not prevented by either peripheral or 3rd ventricle administration of a CRFR1 antagonist, antalarmin, before each restraint. Antalarmin did, however, allow recovery of body weight in the post-stress period. Third ventricle administration of a CRFR2 antagonist, antisauvagine 30, had no effect in RRS rats, but caused sustained weight loss in control animals. Surprisingly, 3rd ventricle administration of the non-selective CRFR antagonist, astressin, caused hypophagia and reversible weight loss in control rats. It had no effect in RRS rats. None of the antagonists modified the corticosterone response to RRS or to mild stress in the post-RRS period, but antalarmin suppressed corticosterone during the period of restraint in Control rats. These results suggest that CRFR1 activation is required for the initiation of events that lead to a prolonged down-regulation of body weight in RRS rats. The sustained reduction in body weight is independent of the severity of hypophagia on the days of restraint and of RRS-induced corticosterone release.
