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 memory processes in a modified passive-avoidance task in mice. The two parameters measured are number of passive-avoidance step-down descents and the active escape latency to reach shock-free zone. Each neurosteroid was administered 60 min before or immediately after the training session, 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 mistakes 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 administered 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 sessions, however, also significantly facilitated memory retention. In addition, the memory-facilitating effects of PS (0.5 mg/kg, s.c.) or DHEAS (1 mg/kg) when administered posttraining are blocked by concurrent administration of haloperidol (0.25 mg/kg, i.p.), a prototype sigma receptor antagonist. These results confirm that both PS and DHEAS facilitate retention of a modified learning task when given either pretraining or posttraining, but not prior to retention test. The pretraining neurosteroid-induced memory modulation do not involve state-dependent effects. These results suggest a role for central sigma receptor in the memory-modulating effects of neurosteroids.