Effects of chronic and acute stressors and CRF on depression-like behavior in mice

The effects of chronic footshock (CFS) on behavioral responses of CD1 mice to acute footshock and restraint were studied in tests commonly used to assess antidepressant treatments. Adult male mice were subjected to 20 min of footshock daily for 14-16 days, and then tested in the tail suspension test (TST) and the forced swim test (FST). CFS treatment did not alter immobility in the TST when mice were tested before the footshock on that day. However, when the TST was performed after the footshock, immobility decreased in both control and CFS mice. In the FST, chronic footshock significantly increased the time spent floating when mice were tested before footshock on that day. However, when the FST was performed immediately after the footshock, floating decreased in the CFS mice, but not in previously unshocked mice. Restraint, shortly before the FST, decreased floating in both CFS and unshocked mice. Thus, CFS induced depression-like activity in the FST, but not in the TST, whereas acute footshock or restraint immediately before testing induced antidepressant-like effects in both the TST and the FST. In unshocked mice, intracerebroventricular corticotropin-releasing factor (CRF) consistently decreased immobility in the TST and the FST, with significant effects at the 100ng dose. The same dose of CRF depressed activity in the open field, so that these changes in immobility are unlikely to reflect a change in overall activity. CRF thus mimicked the effects of the acute stressors in the TST and the FST. Responses to icv CRF were attenuated by chronic footshock suggesting that CFS desensitizes the brain to CRF. CFS treatment did not alter basal concentrations of ACTH and corticosterone in blood plasma. Acute footshock increased the plasma concentrations of the hormones but in CFS mice these responses were attenuated, significantly for plasma ACTH. Acute footshock activated brain dopamine, norepinephrine and serotonin metabolism, and increased tryptophan concentrations in the brain. In CFS mice, these responses were attenuated, significantly for hypothalamic NE.