Behavioral responses to stress are intact in CRF-deficient mice

Corticotropin-releasing factor (CRF) has been implicated in endocrine and b ehavioral responses associated with stress. Fire have now studied the behav ior of mice lacking the CRF gene (CRFko), comparing them to wild-type (WT) mice. Behaviors were observed in untreated mice, as well as following restr aint or intraperitoneal administration of mouse interleukin-1 beta (mIL-1 b eta). In the multicompartment chamber (MCC), the behaviors of CRFko and WT mice were very similar, and prior restraint and IL-LP induced similar decre ases in stimulus-contact times in both genotypes. In the elevated plus maze (EPM), restraint decreased the number of open arm entries but the behavior of both genotypes was very similar. In the open field (OF), the changes in locomotor activity in response to restraint were similar in both genotypes , although CRFko mice displayed slightly increased locomotor activity compa red to WT mice. In both the MCC and the EPM, grooming behavior was increase d by restraint, and was higher in the CRFko than in the WT mice. Compared t o WT mice, CRFko mice had lower basal plasma concentrations of corticostero ne which did not increase significantly following footshock. Thus, CRFko mi ce showed a clear dichotomy; the stress-related activation of the hypothala mo-pituitary-adrenal (HPA) axis was absent, whereas the stress-related beha vioral responses thought to be mediated by brain CRF were unaffected. These results suggest that when mice develop in the absence of CRF, another fact or (or factors) assumes the behavioral functions normally ascribed to brain CRF, but not activation of the HPA axis. Alternatively, the natural modula tor of behavior may not be CRF, but some other molecule that can act on rec eptors sensitive to CRF. Thus, redundant CNS mechanisms appear to be involv ed in stress-related behaviors. (C) 1999 Elsevier Science B.V. All rights r eserved.