Abstract | RATIONALE: 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.
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Authors | Matthias Vandesquille, Ali Krazem, Caroline Louis, Pierre Lestage, Daniel Béracochéa |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 215
Issue 4
Pg. 709-20
(Jun 2011)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 21274701
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzothiadiazines
- Excitatory Amino Acid Antagonists
- Receptors, AMPA
- S18986-1
- Memantine
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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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