Age and sex differences in motivation and spatial working memory in 3xTg-AD mice in the Hebb-Williams maze

The 3xTg-AD mouse model of Alzheimer's disease (AD) has both amyloid beta plaque and tau tangle pathology. However, the results of behavioural testing with these mice have been inconsistent due to age- and sex-related differences, as well as differences in the difficulty of the tests used to measure cognitive function. In order to better understand the sex- and age-related spatial working memory deficits in the 3xTg-AD mice compared to their B6129S/F2 wildtype controls, we tested 4 and 7-month-old males and females and 13-month-old females in the Hebb-Williams maze. In the acquisition phase, the 3xTg-AD mice performed better than the WT controls, but the females of both genotypes showed motivational deficits; often returning to the start box and not eating the food reward, thus taking longer than males to meet the criterion for acquisition. The 3xTg-AD mice showed more working memory deficits than WT mice during the test phase, and the difference increased as the problems increased in difficulty. The results of this study indicate that female 3xTg-AD mice may have motivational deficits in tests using food reward and that the cognitive deficits of the 3xTg-AD mice are not apparent when the tests are too easy; the more difficult the task, the more deficits are shown in the 3xTg-AD mice compared to WT controls. Thus, the inconsistency in previous results may result from differences in motivation and in test difficulty and these must be considered when evaluating cognitive deficits in the 3xTg-AD mice.