The effects of corticotrophin releasing factor (CRF) and handling stress on behavior in the elevated plus-maze test of anxiety

The effects on rodent anxiety of corticotrophin releasing factor (CRF), common experimental stressors and the CRF receptor blocker, α-helical CRF, were measured using the hole board and elevated plus-maze tests. Centrally administered (intracerebroventricular, i.c.v.) CRF increased anxiety in an anxioselective manner. α-Helical CRF (i.c.v) antagonized the effects of CRF, implicating central CRF receptors. Common experimental stressors, such as surgical implantation of cannulas and intraperitoneal injections of saline also selectively increased anxiety in the plus maze. Endogenous CRF binding to central CRF receptors probably mediates the anxiogenic effects of stressors, since α-helical CRF reversed the increased anxiety following surgery. Finally, repeated gentle handling seemed to blunt the anxiogenic effect of CRF. Handling also altered the effect of CRF on behavior, creating an apparently CRF-mediated suppression of rearing and exploration which was not present in rats not stressed with repeated handling. Together the data suggest a modifiable modulatory role of CRF in rodent anxiety. The findings also suggest that careful attention should be paid to stress history when examining the role of CRF in rodent behavior.