The neurosteroid pregnenolone sulfate blocks NMDA antagonist-induced deficits in a passive avoidance memory task

Chantal Mathis, Steven M. Paul, Jacqueline N. Crawley

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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.

Original languageEnglish
Pages (from-to)201-206
Number of pages6
JournalPsychopharmacology
Volume116
Issue number2
DOIs
StatePublished - Oct 1 1994
Externally publishedYes

Keywords

  • Amnesia
  • Ataxia
  • Memory
  • NMDA receptor
  • Neurosteroid
  • Rat

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