The temperature of the test environment impacts the results derived from laboratory mice

Only one drug in ten that holds the potential for being useful in humans because of the results of tests with mice proves to so be. One obvious reason is that mice are not humans even though we are both mammals. Another reason is less obvious. Human patients can be afforded, if they wish and have the means available, significant creature comforts; lab mice are not. One major difference is the affect of the temperature of the environment in which each finds itself.

Lab mice prefer a temperature of 30 degrees C, plus a little. However, in order to address their aggressive tendencies, laboratories are normally kept 5-10 degrees below that. The result, of course, is that they eat more to generate calories and/or body fat to stay warm, which changes their physiology. In turn, this change alters how they metabolize drugs (or any other substance being tested [e.g., potential toxic substances]).

Researchers decided to explore what happens if they allow mice to address lower temperatures as they would in the real world, by building nests. Since no one knows how much nesting material is needed for a mouse to build an appropriate nest, the researchers decided that the question needed to be addressed. The researchers took 36 male and 36 female mice from three strains commonly used in drug trials and set up an experiment. Two cages were connected by a narrow tube. One cage was kept constant at one of six temperatures between 20C and 35C (20, 23, 26, 29, 32, or 35°C); the other cage (the "nesting cage") was kept at 20C, but supplied with up to 10 grams of finely shredded paper (0, 2, 4, 6, 8, or 10 g). The issue to be addressed was: Would the mice rather build a nest in the cooler cage or move to the warmer cage (the mice could also bring nesting material with them into the warmer cage).

The preferences differed slightly between strains and between gender. Females preferred warmer temperatures (it was assumed because of their thinner layer of body fat). Overall, no single set of conditions was optimal to all the mice. With little nesting material around, the mice would carry the paper that was present into the warmer cage. But, if a mouse had access to at least 6 grams of shredded paper in the cooler cage, then many preferred to stay and build a nest in the cooler cage.

While more detailed data needs to be developed, this first-of-its-kind assessment showed that to optimize test results from mice, a more sophisticated approach is needed to their test environment in order to obtain optimum results by reducing the adverse effect of thermal stress. As the researchers noted, when evaluating the results, "[the] results suggest that under normal laboratory temperatures, mice should be provided with no less than 6 grams of nesting material, but up to 10 grams may be needed to alleviate thermal distress under typical temperatures."

The report can be found at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032799.