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.
Reddy
D S
DS
Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, India.
Kulkarni
S K
SK
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D011284:Pregnenolone / Q000494:pharmacology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D012153:Retention, Psychology / Q000187:drug effects*
D018492:Dopamine Antagonists; D017480:Receptors, sigma; C018370:pregnenolone sulfate; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D006220:Haloperidol