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Drug effects of ketamine in mice can depend on the sex of the human experimenter, study finds

Many researchers who work with mice can tell you that mice behave differently depending on who is handling them. Anecdotal reports and some existing scientific reports indicate that mice tend to be more fearful and uptight around men, and relaxed and comfortable around women. Whether this behavior actually affects research results though, remains a sort of the elephant in the room that not many people seem to want to address.

Now, researchers at the University of Maryland School of Medicine (UMSOM) have shown that mice respond more to the antidepressant effects of the drug ketamine when administered by men and not by women. The group demonstrated that the response of mice detected in a specific region of their brain from handling by a man is essential for ketamine’s effect to work. Then, the researchers identified the mechanism behind this response.

The researchers say that while the influence of the sex of the scientist administering ketamine is not directly relevant to the human response to ketamine, the brain mechanism underlying their findings could help determine why some people do not respond to ketamine anti-depressant therapy and suggest ways to potentially make this therapy work better for those patients who do not respond well.

The findings were published on August 30 in Nature Neuroscience.

“Our findings in mice suggests that activating a specific stress circuit in the brain may be a way to improve ketamine treatment. Our thought is that you may be able to provide a more robust antidepressant effect if you combine the ketamine with activation of this brain region, either a drug that spurs this process in the brain or even some sort of specific stressor,” said Todd Gould, MD, Professor of Psychiatry at UMSOM.

Dr. Gould’s team anecdotally noticed that ketamine’s antidepressant-like effects only seemed to work consistently when male researchers administered the treatment to mice. The team reached out to other labs studying mouse responses to ketamine, who reported the same issues, but no one had yet systematically documented the phenomena and investigated the cause. At the time, most of Dr. Gould’s team was women and so figuring out why the experiments did not work when women performed them was essential to the team getting workable data, so they could move forward with project.

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