Effects of Ketamine in Mice Depends on the Sex of the Experimenter

A Stress response in the brain is essential for ketamine’s antidepressant response in mice suggesting new ways to improve antidepressant therapy for patients who do not respond to the treatment
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 (Unsplash)
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 (Unsplash)

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 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 (Unsplash)
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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.

Ketamine’s antidepressant-like effects only seemed to work consistently when male researchers administered the treatment to mice (Unsplash)
Ketamine’s antidepressant-like effects only seemed to work consistently when male researchers administered the treatment to mice (Unsplash)

Dr. Todd Gould’s team at University of Maryland School of Medicine, 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.

The mice preferred spending more time around T-shirts and cotton swabs that came from women rather than men (Unsplash)
The mice preferred spending more time around T-shirts and cotton swabs that came from women rather than men (Unsplash)

To look into this, they began by observing mouse preference for being around T-shirts or cotton swabs rubbed on the wrists, elbow, or behind the ear that came from men versus women. The mice preferred spending more time around T-shirts and cotton swabs that came from women rather than men. When the researchers used a chemical to block the smell of the mice, they no longer preferred women’s T-shirts or cotton swabs over men’s.

“Compared to humans, mouse sense of smell and their sensitivity to pheromones (airborne hormones) are more keenly developed, so it’s not surprising that they respond differently to many smells, including those of men compared to women,” said Dr. Gould.

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 (Unsplash)
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The researchers investigated several factors potentially involved in mediating ketamine’s response in mice (Unsplash)
The researchers investigated several factors potentially involved in mediating ketamine’s response in mice (Unsplash)

Next, they confirmed the original anecdotal findings with a systematic experiment using many researchers to verify that mice responded to ketamine when administered men, but not by women. Then, the researchers wanted to understand the mechanism behind why the mice behave this way. The researchers investigated several factors potentially involved in mediating ketamine’s response in mice, but ultimately settled on one: corticotropin-releasing factor (CRF). CRF is located region of the brain, known as the hippocampus, responsible for learning and memory that had previously been associated with depression. When the researchers had women administer the ketamine along with an injection of CRF, the mice finally responded to ketamine as if they were being treated with an antidepressant. (NS/Newswise)

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