It turns out that the ``gender'' of the person who administers the drug to the mouse affects the experimental results
When conducting an experiment, researchers carefully consider the experimental method so that factors other than what they want to investigate do not affect the experimental results, but sometimes the results are influenced by unexpected factors. A new research team at the University of Maryland in the United States has discovered that 'the 'gender' of the person administering the drug to the mouse affected the experimental results.'
Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor | Nature Neuroscience
2022 News - Effects of Drugs in Mice can Depend on the Sex of the Human Experimenter | University of Maryland School of Medicine
Scientists Discover That a Surprising Factor Improved The Effects of Ketamine in Mice : ScienceAlert
A research team led by Todd Gould, a professor of psychiatry at the University of Maryland School of Medicine, conducted animal experiments on ketamine , which is attracting attention as a fast-acting antidepressant. It is a strange phenomenon that the treatment effect is consistently shown in women, but it may not be as effective in women. The research team also contacted other laboratories about the phenomenon that the sex of the experimenter affects the experimental results, but there was no research team that systematically documented this phenomenon.
desipramine , which is a different type of antidepressant from ketamine, did not change its effect depending on the gender of the experimenter, and changing the administration method did not affect the results. Since the gender of the experimenter does not change the nature of ketamine itself, the research team thought that the series of results was related to 'how ketamine works in the body of mice.'
Therefore, the research team investigated why the sex of the experimenter administering ketamine affects the results. First, when we conducted a mouse stress test focusing on the 'smell' of men and women, it was found that mice prefer the smell of women to the smell of men. In addition, it was revealed that the presence of male experimenter's odor-soaked clothing caused signs of anxiety, pain, and depression in mice. ``Mice have a more acute sense of smell and sensitivity to pheromones than humans, so it's no surprise that mice respond differently to many odors, including men, than women,'' Gould said.
The research team then conducted a blinded, randomized trial with an equal mix of male and female experimenters, again finding that ketamine's antidepressant effects were stronger in male experimenters and weaker in female experimenters. confirmed. In addition,
Investigating multiple factors that may affect the action of ketamine in mice, the research team found that the activation of corticotropic hormone releasing factor (CRF) neurons is the reason why the gender of the experimenter influences the effects of ketamine. I found out that it is. When female experimenters administered CRF together with ketamine to mice, it was reported that the therapeutic effects of ketamine appeared similar to those of male experimenters.
A 2014 study found that laboratory mice and rats were stressed by the presence of a male researcher and induced a stress-responsive analgesic effect. The results of this study also suggest that the male experimenter's odor stresses the mice, activates CRF neurons and CRF circuits, and enhances the stress response, thereby enhancing the effects of ketamine.
This research not only reveals the hidden factors that influence the results of animal experiments, but also has the potential to be applied to treatments using ketamine. ``Our findings in mice suggest that activating specific stress circuits in the brain may improve ketamine treatment,'' Gould said. He argues that combining ketamine with activation of brain regions may have potent antidepressant effects.
The study's first author, Polymnia Georgiou, added: 'Some people have high CRF levels, others have low CRF levels, but even those who do not respond well to antidepressant treatment with ketamine seem to induce the effects of ketamine. I think it might be effective if I could administer a chemical substance related to CRF. It may last longer,' he said.
On the other hand, Science Alert, a scientific media, points out that many of the results of experiments using animals cannot be applied to humans, so experiments to confirm the relationship between ketamine and CRF are necessary in humans.
Georgiou et al. warn that the sex of the experimenter is not the only factor that distorts the results of animal experiments, but that factors such as cage conditions, overall stress, circadian rhythms, and the experimenter's diet also affect the results. Did.