Rats exposed to 3 h 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 postrestraint period.
Weight loss was not prevented by either peripheral or third-ventricle administration of a CRFR1 antagonist,
antalarmin, before each restraint.
Antalarmin did, however, allow recovery of
body weight in the poststress 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, third-ventricle administration of the nonselective 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.