Journal
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 21, Issue 2, Pages 211-215Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2010.09.010
Keywords
Pregnenolone sulfate; Steroid enantiomers; Memory; Y-maze; NR1 subunit; Hippocampus; NMDA receptors
Funding
- Institut National de La Sante et de la Recherche Medicate, GIS Longevite [A04025LS, L0201]
- Agence Nationale de la Recherche (ANR) [07-JCJC-0108-01]
- United States National Institutes of Health [GM 47969]
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This study examined the role of forebrain N-methyl-D-aspartate receptors (NMDA-Rs) in the promnesiant effects of natural (+) pregnenolone sulfate (PREGS) and its synthetic (-) enantiomer ent-PREGS in young adult mice. Using the two-trial arm discrimination task in a Y-maze, PREGS and ent-PREGS administration to control mice increased memory performances. In mice with a knock-out of the NR1 subunit of NMDA-Rs in the forebrain, the promnesiant effect of ent-PREGS was maintained whereas the activity of PREGS was lost. Memory enhancement by PREGS involves the NMDA-R activity in the hippocampal CA1 area and possibly in some locations of the cortical layers, whereas ent-PREGS acts independently of NMDA-R function. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.
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