EFFECT OF AGE AND STRAIN ON WORKING MEMORY IN MICE AS MEASURED BY WIN-SHIFT PARADIGM

Working memory is disrupted in Alzheimer's disease and stroke; therefore, any therapeutic drug should restore deficits in working memory. The win-shift foraging paradigm has been demonstrated to be a model of working memory in rats. In the present study, this paradigm was adapted to mice because of the greater ease and economy of testing potential drugs in mice and the wider availability of strains of aged mice with naturally occurring working memory deficits. This study has demonstrated strain differences in the working memory trace and that age induces a deficit that can be detected at 11 months of age in mice. Tacrine and physostigmine enhance the memory trace in normal mice and physostigmine can reverse age-induced working memory deficits in subjects with mild and moderate deficits but not in subjects with severe deficits.