The effect of antagonism of CRF receptors in areas adjacent to the third ventricle during repeated restraint

Corticotropin-releasing factor (CRF) initiates many of the immunologic, endocrine, autonomic, metabolic and behavioral responses to stress through activation of central and peripheral CRF receptors (CRFR). The two types of CRFR, CRFR1 and CRFR2, are differentially distributed throughout the brain and mediate different aspects of the stress response. Exposure to repeated restraint (RR), a model of acute stress, induces chronic changes such as a sustained reduction in body weight and hyperreactivity of the endocrine response to mild stressors applied in the post-RR period. In the first Experiment, we found that mice exposed to RR exhibit increased anxiety-like behavior in the post-RR period. In the second set of Experiments we found that antagonism CRFR1 during RR results in attenuation of the sustained decrease in body weight while antagonism of CRFR2 prevents stress-induced hypophagia. These results imply that activation of CRFR1 is necessary to induce the chronic effects of RR on body weight.