The effects of repeated restraint stress on energy balance and behavior of mice with selective deletion of CRF receptors

Mice subjected to restraint stress (RRS) daily for 3 days lose weight. Once stress ends they are slow to recover the weight loss and exhibit increased anxiety and hypothalamuspituitaryadrenal (HPA) activity in response to novel stressors. We tested the effect of RRS in mice deficient in corticotropin releasing factor receptor one (CRFR1-KO) or two (CRFR2-KO). Wild type (WT) and CRFR2-KO, but not CRFR1-KO, mice lost weight during RRS. All adrenalectomised mice lost weight and CRFR2-KO controls stopped gaining weight on the days of RRS. WT RRS mice returned to the weight of their controls 8 days after restraint. CRFR2-KO mice showed high levels of anxiety in an elevated plus maze (EPM) 11 days after RRS and in a light/dark choice test 14 days after RRS. CRFR1-KO mice displayed low anxiety in both tests, but RRS decreased EPM exploration. By contrast, exploration increased in RRS ADX mice. Testing in the EPM increased serum corticosterone level in all WT and CRFR2-KO mice. Corticosterone increased in RRS CRFR1-KO mice compared with their controls. These results suggest that CRFR1 are required for stress-induced weight loss, but that hyper-reactivity of the HPA axis in RRS mice exposed to a subsequent novel stress is independent of CRFR1.