Swimming in Circles

Determining the role of a drug or gene on our ability to learn is a truly difficult task. We all learn in slightly different ways. Add in disease states (such as Alzheimer’s or Parkinson’s), or addictions (such as alcohol or drug), or different stages of life, and it becomes apparent that this is a very complicated issue, where “one size” does not fit all.

Yet, many researchers attempt to distill this complex issue down to a few simple components when they test the roles of drugs and genes using an apparatus known as the Morris Water Maze (MWM). The MWM was developed in 1981 as a simple way to assess spatial learning and memory. A mouse or rat placed in a large circular metal tank, filled with opaque water, must swim around the tank to find a hidden platform, using distant visual clues. Many factors are measured, including swim speed, route, visual learning recall, and time until the subject “gives up.” It is one of the most prevalent tests used, appearing in over 5,000 publications since 1981.

It is also a very stressful test, and one that is subject to many limitations and operator biases. To name but a few of the limitations: Mice are not strong swimmers and have oils in their coat to keep them buoyant. While rats will typically start swimming as soon as they are placed in the water, mice may float for variable amounts of time, until they decide they absolutely must swim. The MWM is highly reliant on visual ability, particularly distance vision. Yet, in many strains of rats and mice, their vision has been affected by genetic manipulations. Animals who have gone through the test previously may leave distinct scent trails in the water, allowing subsequent test subjects to go through the test more quickly. Mice, in particular, are prone to becoming hypothermic. Even the way the animal is placed in the water can affect the results.

Beyond all of the confounding variables is the simple fact that a mouse or rat is being placed in a very unnatural and stressful situation, with no means of escape. Even after they find the hidden platform, they are often required to repeat the procedure several more times on the same day. Given the existence of less stressful (and potentially more reliable) tests of spatial learning and memory, use of the MWM does not embody the “refinement” component of the 3Rs of animal research—improving scientific procedures to minimize actual or potential pain, suffering, or distress and/or improve animal welfare in situations where use of animals is unavoidable.

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