Hypothermia in mice tested in Morris water maze.

The Morris water maze, one of the most common behavioral tasks to assess learning and memory in rodents, exposes the animals to cold water for a few minutes. Unlike rats, young healthy mice can become severely hypothermic during the task. Five swims of 45 s in 20 degrees C water with 30s between the trials was enough to cause up to 9 degrees C drop in the rectal temperature. The decline in core temperature was accompanied by slowing of the swimming speed. Moreover, the effect was dependent on the sex and genotype of the mice, such that females were more susceptible to hypothermia than males and transgenic mice carrying Alzheimer-associated APP and PS1 mutations more vulnerable than their nontransgenic littermates. Raising the water temperature from 20 to 24 degrees C alleviated the hypothermia, but did not remove the significant drop in core temperature when using 30-s inter-trial interval. However, increasing the break from 30 s to 13 min removed the net cooling effect of five trials on the core temperature and swimming speed. We conclude that the currently most common water maze protocol renders mice hypothermic, which may confound the test results, especially when transgenic female mice are used. We recommend monitoring of the swimming speed on a trial-by-trial basis and using longer inter-trial intervals.