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S 18986 reverses spatial working memory impairments in aged mice: comparison with memantine.

AbstractRATIONALE:
Normal or pathological ageing is characterized by working-memory dysfunction paired with a marked reduction in several neurotransmitters activity. The development of therapeutic strategy centered on the glutamatergic system known to bear a critical role in cognitive functions, is therefore of major importance in the treatment of mild forms of AD or age-related memory dysfunctions.
OBJECTIVES:
In Experiment 1, we investigated the effects of ageing on spatial working memory measured by sequential alternation (SA). Thus, the decay of alternation rates over a series of trials separated by varying intertrial temporal intervals (ITI, from 5 sec to 180 sec) was studied in mice of different age groups. In Experiment 2, we investigated the memory-enhancing potential of S 18986--a modulator of AMPA receptors--on age-related SA impairments, in comparison with memantine--an antagonist of NMDA receptors--.
RESULTS:
In Experiment 1, aged mice responded at chance with shorter ITI's and exhibited greater levels of interference in the SA task as compared to young adult mice. In Experiment 2, (1) S 18986 at 0.03 and 0.1 mg/kg reversed the memory deficit in aged mice but did not modify performance in young adult mice; (2) memantine at 10 mg/kg also increased SA rates in aged mice but did not improve performance in young adult mice.
CONCLUSION:
The SA task is a useful tool to reveal age-induced time-dependent working memory impairments. As compared to memantine, S 18986--a compound targeting AMPA receptors--contributes a valuable therapy in the treatment of age-related cognitive dysfunctions or mild forms of AD.
AuthorsMatthias Vandesquille, Ali Krazem, Caroline Louis, Pierre Lestage, Daniel Béracochéa
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 215 Issue 4 Pg. 709-20 (Jun 2011) ISSN: 1432-2072 [Electronic] Germany
PMID21274701 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzothiadiazines
  • Excitatory Amino Acid Antagonists
  • Receptors, AMPA
  • S18986-1
  • Memantine
Topics
  • Aging (drug effects, metabolism, psychology)
  • Alzheimer Disease (drug therapy)
  • Animals
  • Behavior, Animal (drug effects)
  • Benzothiadiazines (administration & dosage, therapeutic use)
  • Excitatory Amino Acid Antagonists (administration & dosage, therapeutic use)
  • Male
  • Maze Learning (drug effects)
  • Memantine (administration & dosage, therapeutic use)
  • Memory Disorders (metabolism, prevention & control, psychology)
  • Memory, Short-Term (drug effects)
  • Mice
  • Mice, Inbred C57BL
  • Receptors, AMPA (antagonists & inhibitors, metabolism)

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