Deciphering Morris water maze behavior in aging Sprague-Dawley rats: Taking care of age- and sex-specific effects in preclinical research

Abstract

As aging is recognized as one of the risk factors for cognitive impairment contributing to thedecline in daily functioning in the aging population, its impact should be better assessed and characterizedin preclinical models. Therefore, we investigated the differences in learning and memory behavior in the Morris water maze (MWM) between aging and young adults. 15- and 7-month-old Sprague-Dawley rats of both sexes were subjected to extended behavioral battery including the MWM. The animals were trained to find the platform for 4 days. Further, probe test was performed in which platform was removed and the animals were allowed to explore MWM. Aging animals covered greater distance than young adults during the training phase. Only young adult males and females covered shorter distance on training day 4 vs day 1. In addition, an interaction between sex and age for distance was observed during the training phase. On training day 2, aging males showed longer latency to find the platform compared to young adult males. Aging and young adult females showed higher percentage of peripheral time than young adult males on the training day 4. In the probe test, the latency to find the platform did not differ between groups, but the young adult females traveled greater distance than the young adult males. In addition, these animals had higher percentage of peripheral time compared to all other groups, except for the young adult males, where the difference was at trend level. Learning deficits in aging animals were partially associated with motor impairments in both sexes and were pronounced in aging males at the beginning of the training phase. Sex-specific differences were reflected in the increased anxiety observed in females, which may also contribute to the reduced learning performance. In the probe test, young adult females showed the hyperactivity characteristic of this age group, but also increased anxiety. The latter was reversed in the aging females, indicating their possible emotional maturation. The complex cognitive behavior in older age, which is influenced by sex, should be taken into account in drug discovery research of dementia and other age-related diseases