Psychopharmacology

, Volume 193, Issue 1, pp 63–73 | Cite as

Improvement of episodic contextual memory by S 18986 in middle-aged mice: comparison with donepezil

  • D. Béracochéa
  • J. N. Philippin
  • S. Meunier
  • P. Morain
  • K. Bernard
Original Investigation

Abstract

Introduction

This study compared the effects of S 18986, a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, to those of donepezil a cholinesterase inhibitor on memory impairments induced by ageing in a contextual serial discrimination (CSD) task in middle-aged mice.

Materials and methods

The CSD task involved the learning of two consecutive discriminations in a four-hole board, each performed on two different floors. This model has been developed to study simultaneously different forms of memory in mice (i.e., episodic-like vs semantic-like forms of memory). We showed that placebo-middle-aged mice (14–15 months old) and placebo-aged subjects (19–20 months old) exhibited a severe memory deficit for the first but not the second discrimination, which was due to an increase in interference, as compared with placebo-treated young mice (5 months old). Middle-aged mice were given (9 days) per os administration of either donepezil, S 18986, or placebo.

Results and discussion

Both 0.3 mg/kg donepezil and 0.1 mg/kg S 18986 reversed the deficit of middle-aged mice through a significant increase in contextually correct responses and in parallel a tendency to reduce interfering responses.

Conclusion

Overall, S 18986 emerges as having a beneficial impact on contextual memory processes in middle-aged mice.

Keywords

Ageing Mice Contextual memory Episodic memory Semantic memory S 18986 Donepezil AMPA receptors 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • D. Béracochéa
    • 1
  • J. N. Philippin
    • 1
  • S. Meunier
    • 2
  • P. Morain
    • 2
  • K. Bernard
    • 2
  1. 1.Centre de Neurosciences Intégratives et Cognitives(CNIC), UMR CNRS 5228, Bat Biologie AnimaleUniv. Bordeaux 1 et 2Talence-cedexFrance
  2. 2.Institut de Recherches Internationales Servier (IRIS)Courbevoie cedexFrance

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