Oct. 15, 2008 -- Female lab mice can respond quite differently to male mice when it comes to anxiety, a new study has found, which could have important implications for scientific research.
Neuroscientist Tim Karl of the Garvan Institute of Medical Research and colleagues report their findings in the European Journal of Neuroscience.
"In the end it has general implications for how to use animal models," said Karl. "At the moment male mice are used to apply findings to both male and female humans. That's definitely not the ideal situation."
Karl and colleagues studied the impact of a neurotransmitter known as neuropeptide Y (NPY), which helps lower anxiety levels as well as influences aggression and appetite.
Previous studies have shown that when mice are given a drug that mimics NPY it reduces anxiety when they are put under stress. Studies have also shown that mice genetically modified to lack the gene for NPY are more prone to anxiety than normal mice. But these previous studies used male mice, which are the standard laboratory animal.
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Karl and colleagues studied the behavior of both female and male mice that had their NPY gene knocked out. To their surprise they found that while both sexes were more anxious than normal mice, lacking the NPY gene made the male mice more anxious than female mice.
"For the males, knocking out the NPY gene has a much bigger effect than if you knock it out in female mice," said Karl.
The findings add to a growing body of evidence that both sexes should be used in lab tests. It also suggests that both drug and genetic studies should be done to get the full picture of what is going on.
Male mice are thought to be more reliable as lab animals because the oestrus cycles of female mice can interfere with findings, Karl said. But he adds it is possible to use females when they are all in the same stage of oestrus.
It may be possible to use NPY to treat anxiety in humans, but to date 80 to 90 percent of NPY research has been done in male mice. Even if researchers include female mice, the findings by Karl and colleagues suggest further care will be needed in applying the mouse model to humans.
The findings that female mice without the NPY gene are less prone to anxiety than males appears to go against what is known in humans, where females are more likely to develop anxiety disorders. But this does not mean that female mice are not useful as a model in studying anxiety in humans.
Indeed, given there is a difference between the sexes in humans, it is appropriate for an animal model to also show a difference -- even if it is an opposite trend.
Karl said this needs to be used as a tool when interpreting results of studies.
"You have to be very careful about using animal models, but sometimes they're the only tool we have to work on certain diseases," he said.
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