The anorectic effects of CRH and restraint stress decrease with repeated exposures.

Intracerebroventricular (icv) administration of corticotropin-releasing hormone (CRH) or exposure to a restraint stressor causes acute anorexia in rats. However, the effects on food intake of repeated injections of CRH or repeated exposures to restraint stress have not been previously reported. As the effects of these more chronic CRH and stress treatments may be of greater relevance to emerging hypotheses of the pathogenesis of human eating and affective disorders, we measured the changes in food intake and body weight of rats after repeated central injections of CRH. In two experiments using two different daily dosages of CRH and two different schedules of administration, we found that the anorectic effect of CRH decreased over repeated injections. Weight gain was slowed significantly only in the high-dose experiment. Rats may become tolerant to the anorectic effects of CRH delivered by repeated icv injections. These findings have important implications for hypothesized mechanisms of anorexia nervosa and/or depression.