Corticotropin-releasing factor receptor antagonist infused into the locus coeruleus attenuates immobilization stress-induced defensive withdrawal in rats

It has been proposed that corticotropin-releasing factor (CRF) released during stress in the region of the locus coeruleus (LC) induces changes in behavior that are typical indices of anxiety. The experiments tested the ability of a CRF antagonist, hCRF_9–41, to attenuate stress-induced defensive withdrawal in rats. 1 μg of hCRF in 300 nl was infused bilaterally in the LC of rats 10 min prior to 30 min immobilization. The apparatus consisted of a small chamber set on one side of a 1 m open field, into which the rat was placed to start the test. Restraint induced defensive withdrawal in rats familiar with the apparatus and significantly increased latency time to emerge from the chamber, total time and mean time spent in the chamber. Infusion of hCRF into the LC prior to restraint significantly decreased total and mean time spent in the chamber comparing to stressed animals. These results are consistent with anatomical, electrophysiological and neurochemical evidence that CRF receptors located in, or close to, the LC region influence behaviors induced by stress.