Actually, the scientists from the University of Maryland wanted to test how ketamine affects depressed mice. Studies had already suggested a soothing effect. However, the team led by Tedd Gould was unable to replicate his own results and those of other research groups and began to investigate.
In retrospect, a clear pattern emerged: if a male test subject administered ketamine to mice, an antidepressant effect occurred. If, on the other hand, it was a woman, there was no effect. The team already knew that the sex of the experimenter can influence rodents’ stress and behavioral responses. The group wanted to investigate this and started an experiment: At random, either a man or a woman gave the animals ketamine or a placebo. A third person then subjected the rodents to a behavioral test. In fact, to everyone’s surprise, only the mice given the ketamine by a man were less depressed. To be on the safe side, the working group repeated the experiment several times with different people and also at other universities – the result was always the same.
Gould and his colleagues subsequently found that mice dislike male smells and prefer female smells. In addition, the animals were more susceptible to stress when they were handled by a male experimenter. And stress affects ketamine’s effects, the team found: Corticotropin-releasing hormone (CRH) mediates stress responses and is released in the entorhinal cortex in response to male scent. When the researchers increased CRH activity, this increased the antidepressant effect of ketamine. Many other unknown factors could have influenced the results, as the authors point out in »Nature Neuroscience«. However, they recommend specifying the sex of the experimenter in the methods section of animal studies and, if possible, including this variable statistically. The discovery could also lead to new treatment approaches, such as the administration of ketamine in combination with substances that activate the CRH receptor.