The effects of CRF and α-helical CRF on anxiety in normal and hypophysectomized rats

The effect of corticotrophin-releasing factor (CRF) on anxiety in normal and hypophysectomized (HYPOX) rats was investigated. Intracerebroventricular injection (i.c.v.) of 2 μg of CRF increased anxiety in the elevated plus maze test in normal and HYPOX rats. Anxiety was measured as the ratio of time spent in the open arms of the maze to total time spent in all arms of the maze. CRF also reduced head dipping and rearing in the hole board, and the number of entries into the arms of the plus maze. These latter changes in behavior were independent of the changes in anxiety. All behavioral effects of CRF in HYPOX rats were blocked completely by the CRF receptor blocker, α-helical CRF (50 μg). Completeness of hypophysectomy was assessed by measuring plasma corticosterone (CORT) level changes 20 min after i.c.v. CRF (2 μg). CORT levels of all HYPOX rats given CRF were well below (< 1/10th) resting baseline levels of normal rats. Moreover, i.c.v. injection of saline vehicle nearly tripled CORT levels over resting baseline in normal rats, and CRF increased CORT levels 2-fold over vehicle. Taken together, these findings replicate the observation that CRF administered i.c.v. to rats is selectively anxiogenic in the elevated plus maze. They also indicate that the anxiety produced by CRF does not involve activation of the pituitary-adrenal axis. Rather, CRF-induced anxiety depends on the binding of CRF to central nervous system CRF receptors. Finally, the plasma CORT data indicate that i.c.v. injection of saline vehicle is stressful, as is injection of CRF.