Polymnia Georgiou and colleagues accidentally came across an example of researchers skewing a study's results when their lab mice's reactions to ketamine differed depending on the sex of the humans who administered the drug.
They did a randomized trial with a mix of male and female experimenters to make sure it wasn't just a weird fluke. The mice had a better response to the drug when it was handled by men.
The presence of male humans does not change the properties of the drug.
When administered by both males and females, desipramine worked well.
Stressing the mice didn't help them respond to the drug when it was given to them. The sex effect was specific to how the drug works in the mice.
A series of stress tests revealed that the presence of not just human male experimenters but also their clothing caused the mice to display more signs of depression, pain, and anxiety.
Lab rodents become stressed in the presence of men. The presence of male experimenters seemed to have a negative effect on their pain responses.
After some trial and error, Georgiou and the team were able to identify brain activity in an area with known links to depression.
They gave the female experimenters the same hormones as the males and the mice responded the same way.
When administered by males, it works better because the scent of the mice makes the CRF system work better.
Compared to humans, mouse sense of smell and their sensitivity to pheromones are more developed, so it's not surprising that they respond differently to many smells, including those of men.
The findings show that ketamine works with the pathway.
Gould says that their findings show that a stress circuit in the brain may be a way to improve treatment.
It's possible that these results are the missing piece of the puzzle as to why some people respond well to the drug while others don't.
Gould thinks that if you combine the two drugs, you may be able to provide a more robust antidepressant effect.
Many animal model studies don't translate well to humans and this would have to be further tested in humans. This translation problem may be related to the observer effect shown here.
Simple changes to experimental procedures can be used to solve the problem. The male experimenter can stay in the room with the animals before starting the experiment since the effects of males' presence diminish over time. The gender of the experimenter should be stated in the paper.
The sex of an experimenter isn't the only factor that should be taken into account when determining results, according to the team.
Researchers conclude that by investigating these factors, they could help increase the robustness of all biological research by allowing for greater replication of experiments and providing more insights into our shared biology.
The research was published in a journal.
All Rights Reserved © 2024
