The neurosteroid pregnenolone sulfate reduces learning deficits induced by scopolamine and has promnestic effects in mice performing an appetitive learning task |
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Authors: | H. Meziane C. Mathis A. Ungerer S. M. Paul |
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Affiliation: | (1) Laboratoire de Psychophysiologie, ULP, URA-CNRS 1295, 7 rue de L'Université, F-67000 Strasbourg, France;(2) Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, 46285 Indianapolis, IN, USA |
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Abstract: | The effects of the neurosteroid pregnenolone sulfate (PS) on learning as well as on scopolamine-induced learning deficits were studied in Swiss mice using an appetitively reinforced Go-No Go visual discrimination 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, intracerebroventricular (ICV) administration of PS (0.01–10 nmol) dose-dependently blocks learning deficits induced by scopolamine (3 mg/kg), with the most potent effects at the dose of 0.5 nmol PS. In addition to antagonizing the amnestic effects of scopolamine, PS (0.5 nmol ICV) has a memory-enhancing effect, when administered alone after the first training session. Scopolamine (3 mg/kg SC) also produced substantial deficits on retrieval performance in the Go-No Go visual discrimination task, and caused 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 traction reflex test. Such a rapid effect of PS on memory processes may be mediated via NMDA and/or GABAA receptors. |
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Keywords: | Retrieval NMDA receptor GABAA receptor Memory Amnesia Go-No Go visual discrimination Mice |
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