213 116 116 2 2 Dr. Chantal Mathis Steven M. Paul Jacqueline N. Crawley Section on Behavioral Neuropharmacology, Experimental Therapeutics Branch National Institute of Mental Health, National Institutes of Health 20892 Bethesda MD USA Section on Molecular Pharmacology, Clinical Neuroscience Branch National Institute of Mental Health, National Institutes of Health 20892 Bethesda MD USA Laboratoire de Psychophysiologie, ULP, URA CNRS 1295 7 rue de l'Université 67000 Strasbourg France Lilly Research Laboratories, Eli Lilly and Co. 46285 Indianapolis IN USA Abstract The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84–1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84–840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors.
Psychopharmacology – Springer Journals
Published: Oct 1, 1994
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