Effects of Acute and Chronic Stressors and CRF in Rat and Mouse Tests for Depression

Depressive illness is frequently associated with life stress. Corticotropin-releasing factor (CRF) is believed to be a key brain mediator of behaviors associated with stress, and abnormalities in the function of CRF have been associated with depression. Therefore, we have studied the effects of acute and chronic footshock and restraint in tests used in rodents to assess depression-like activity and antidepressant effects: the forced swim test in rats and mice, and the tail suspension test in mice. We also tested the effect of intracerebroventricular (icv) CRF administration. The results were complex. In the forced swim test in rats, acute footshock and restraint reduced floating, whereas chronic footshock increased floating as did icy CRF. However, chronic restraint induced opposite effects, decreasing floating in the forced swim test. The results from mice were significantly different. In the forced swim test, acute footshock and restraint decreased floating, while chronic footshock increased floating, and chronic restraint decreased floating as it did in rats. However, icy CRF decreased floating. The results from the tail-suspension test paralleled those from the forced swim test except that chronic footshock tended to decrease the time spent immobile. Thus in rats, the behavioral effects of the chronic footshock in the forced swim test could be explained by a desensitization of the CRF systems, either decreased activation of CRF, or desensitization of its receptors. However, such an effect cannot explain the responses to restraint, nor the behavioral effects of chronic footshock and restraint in mice.