CRF-deficient mice respond like wild-type mice to hypophagic stimuli

Corticotropin-releasing factor (CRF) has been implicated in physiological processes associated with stress, including changes in feeding behavior. Intracerebroventricular (ICV) administration of CRF and urocortin have been shown to depress feeding, and antagonism of CRF receptors has been reported to attenuate hypophagic responses to many treatments, suggesting that brain CRF may mediate these responses. We have now studied feeding behavior of mice lacking the CRF gene (CRFko), comparing them to wild-type (CRFwt) mice. Feeding was assessed in nondeprived mice by measuring the intake of sweetened milk in a 30-min period and the food pellet intake over 24 h. ICV administration of CRF or urocortin (1 microg, but not lower doses) depressed milk and food pellet intake in normal mice. Physical restraint for 30 min, or administration of mouse interleukin-1beta (mIL-1beta, 100 ng, IP), lipopolysaccharide (LPS, 1 microg, IP), or the serotonergic agonist (d-fenfluramine, 4 mg/kg, IP) reliably reduced milk intake. LPS also reduced food pellet intake. The responses to restraint, IL-1, LPS, and fenfluramine were indistinguishable between the CRFwt and CRFko mice. These results suggest that CRF is not essential for the reduction in sweetened milk intake that occurs following restraint, LPS, IL-1, or d-fenfluramine administration to mice.