Role of corticotropin-releasing factor in forced swimming test

Several aspects of the role of corticotropin-releasing factor (CRF) in the forced swimming test were investigated in this study by using two different administration schedules. I.c.v. microinjection of CRF produced a dose-dependent increase in swimming activity when the administration schedule originally reported for this test to screen antidepressant drugs was followed. The most effective doses were 1 and 3 microg of CRF. A lower dose of CRF (0.5 microg) was also effective when repetitive experimental stress was present. CRF receptor antagonist, alpha-helical CRF-(9-41) (alpha-helical CRF-(9-41)), was able to block CRF-induced increases in swimming in all sessions of the forced swimming test. However, the effects of CRF and CRF receptor antagonist depended on the administration schedule. A decrease in swimming in the forced swimming test was observed when CRF and CRF receptor antagonist were given together, using a different administration schedule. I.c.v. CRF was ineffective and CRF receptor antagonist alone produced an increase in swimming when administered according to this schedule. These behavioural responses were maintained after twelve days without any treatment. The results of the current study suggest that endogenous CRF seems to play a determinant role in behavioural responses in the forced swimming test. The involvement of the level of activation and memory processes in these behavioural responses is discussed.