THE EFFECTS OF NEUROSTEROIDS ON ACQUISITION AND RETENTION OF A MODIFIED PASSIVE-AVOIDANCE LEARNING-TASK IN MICE

This study examined the effects of neurosteroids, pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS), on learning and memo ry processes in a modified passive-avoidance task in mice. The two par ameters measured are number of passive-avoidance step-down descents an d the active escape latency to reach shock-free zone. Each neurosteroi d was administered 60 min before or immediately after the training ses sion, or 60 min before the retention test given 24 h after acquisition . Pretraining injection of PS (0.125-10 mg/kg, s.c.) and DHEAS (0.125- 10 mg/kg, s.c.) decreased the number of mistakes committed on training day but had no effect on the latency measure. Both PS (0.125-10 mg/kg , s.c.) and DHEAS (0.125-10 mg/kg, s.c.) decreased the number of mista kes and latency to reach shock-free zone, in a dose-dependent and bell -shaped manner, following pretraining and posttraining administration schedules. Neurosteroids failed to improve memory performance when adm inistered 60 min before retention testing. Injection of PS (0.5 and 1 mg/kg) or DHEAS (1 and 5 mg/kg) before both the training and test sess ions, however, also significantly facilitated memory retention. In add ition, the memory-facilitating effects of PS (0.5 mg/kg, s.c.) or DHEA S (1 mg/kg) when administered posttraining are blocked by concurrent a dministration of haloperidol (0.25 mg/kg, i.p.), a prototype sigma rec eptor antagonist. These results confirm that both PS and DHEAS facilit ate retention of a modified learning task when given either pretrainin g or posttraining, but not prior to retention test. The pretraining ne urosteroid-induced memory modulation do not involve state-dependent ef fects. These results suggest a role for central sigma receptor in the memory-modulating effects of neurosteroids. (C) 1998 Elsevier Science B.V.