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 prod uced a dose-dependent increase in swimming activity when the administr ation schedule originally reported for this test to screen antidepress ant drugs was followed. The most effective doses were I and 3 mu g of CRF. A lower dose of CRF (0.5 mu g) was also effective when repetitive experimental stress was present. CRF receptor antagonist, alpha-helic al CRF-(9-41) (alpha-helical CRF-(9-41)), was able to block CRF-induce d increases in swimming in all sessions of the forced swimming test. H owever, the effects of CRF and CRF receptor antagonist depended on the administration schedule. A decrease in swimming in the forced swimmin g test was observed when CRF and CRF receptor antagonist were given to gether, using a different administration schedule. I.c.v. CRF was inef fective and CRF receptor antagonist alone produced an increase in swim ming when administered according to this schedule. These behavioural r esponses 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 te st. The involvement of the level of activation and memory processes in these behavioural responses is discussed. (C) 1998 Elsevier Science B .V.