THE NEUROSTEROID PREGNENOLONE SULFATE REDUCES LEARNING-DEFICITS INDUCED BY SCOPOLAMINE AND HAS PROMNESTIC EFFECTS IN MICE PERFORMING AN APPETITIVE LEARNING-TASK

The effects of the neurosteroid pregnenolone sulfate (PS) on learning as well as on scopolamine-induced learning deficits were studied in Sw iss mice using an appetitively reinforced Go-No Go visual discriminati on task. Subcutaneous (SC) administration of scopolamine (0.3-3 mg/kg) after the first session of training dose-dependently impairs learning during the following sessions in this task. Moreover, intracerebroven tricular (ICV) administration of PS (0.01-10 nmol) dose-dependently bl ocks learning deficits induced by scopolamine (3 mg/kg), with the most potent effects at the dose of 0.5 nmol PS. In addition to antagonizin g the amnestic effects of scopolamine, PS (0.5 nmol ICV) has a memory- enhancing effect, when administered alone after the first training ses sion. Scopolamine (3 mg/kg SC) also produced substantial deficits on r etrieval performance in the Go-No Go visual discrimination task, and c aused motor disturbances, when administered 15 min before testing. PS (0.5 nmol ICV) also reduced scopolamine-induced deficits on retrieval but had no effect on scopolamine-induced motor impairments in the trac tion reflex test. Such a rapid effect of PS on memory processes may be mediated via NMDA and/or GABA(A) receptors.