The effects of flumazenil on two way active avoidance and locomotor activity in diazepam-treated rats

The present study was undertaken to determine the effects of chronic flumazenil treatment alone and simultaneously with diazepam on acquisition performance in an active-avoidance task and on locomotor activity in rats. Flumazenil (5, 10 and 20 mg/kg) and diazepam (0.5, 1.0 and 2.0 mg/kg) were administered intraperitoneally to rats before each dairy training session for 5 days. The baseline of avoidance performance was set to approximately 50% and responses were expressed as acquisition rate. Locomotor activity of the rats was simultaneously recorded but only following the first training session. Diazepam decreased acquisition rate between the dose range used. Flumazenil had no effect on the acquisition rate of naive rats but reversed low dose diazepam-induced learning and memory impairment. Diazepam induced locomotor depression within the same dose range that decreased acquisition rate. Flumazenil had no effect on locomotor activity, but reversed the locomotor depressant effect of diazepam. The striking contradiction with previous data that flumazenil has no effect on learning-memory processing is discussed. (C) 1999 Elsevier Science B.V./ECNP. All rights reserved.