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S 18986 reverses spatial working memory impairments in aged mice: comparison with memantine
Matthias Vandesquille1, Ali Krazem, Caroline Louis
1Institut de Neurosciences Intégratives et Cognitives d'Aquitaine, Universités de Bordeaux, IMR CNRS 5287, Avenue des Facultés, 33405, Talence, France.
Psychopharmacology
|January 29, 2011
Summary
A new compound, S 18986, targeting AMPA receptors, effectively improved spatial working memory in aged mice. This offers a promising therapeutic strategy for age-related cognitive decline and mild Alzheimer's disease.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Aging impairs working memory and neurotransmitter activity.
- The glutamatergic system is crucial for cognitive function.
- Therapeutic strategies targeting this system are important for age-related memory issues and mild Alzheimer's disease.
Purpose of the Study:
- To assess the impact of aging on spatial working memory using the sequential alternation task.
- To evaluate the memory-enhancing effects of S 18986, an AMPA receptor modulator.
- To compare S 18986 with memantine, an NMDA receptor antagonist, in aged mice.
Main Methods:
- Spatial working memory was measured by sequential alternation (SA) in young and aged mice.
- The effect of varying intertrial intervals (ITI) on SA performance was analyzed.
- Mice were treated with S 18986 or memantine to assess their impact on SA performance.
Main Results:
- Aged mice showed impaired SA performance, especially with shorter ITIs, indicating age-related working memory deficits.
- S 18986 (0.03 and 0.1 mg/kg) significantly improved SA performance in aged mice.
- Memantine (10 mg/kg) also improved SA performance in aged mice, but S 18986 showed greater therapeutic potential.
Conclusions:
- The SA task effectively identifies age-related, time-dependent working memory impairments.
- S 18986 demonstrates significant potential as a therapeutic agent for age-related cognitive dysfunction.
- S 18986 may offer a valuable treatment option for mild Alzheimer's disease compared to memantine.
