Ketamine fights depression in mice – when a *male researcher* administers it.

Nature dives into some pretty weird sex-based results in pharmacological studies of ketamine:

The findings, presented on 14 November at the Society for Neuroscience (SfN) meeting in Washington DC, only deepen the mystery of how ketamine, which has powerful mood-lifting properties, interacts with the brain. They also raise questions about the reproducibility of behavioural experiments in mice.

Polymnia Georgiou, a neuroscientist at the University of Maryland in Baltimore, is one of them. In 2015, a male colleague asked her to run some experiments for him while he was out of town, including a standard way of testing antidepressants called the forced-swim test. In this assay, researchers inject healthy mice with a drug, place them into a tank of water and measure how long they swim before they give up and wait for someone to rescue them.

Antidepressants can cause healthy mice to swim for longer than their untreated counterparts, which is what Georgiou’s male colleague found during his experiments using ketamine.

When she and three female and four male researchers investigated this disconnect by performing the experiments, they discovered that the ketamine acted as an antidepressant only when it was administered by men.

Suspecting that scent was involved, the researchers put the animals inside a fume hood so that the mice couldn’t smell who was injecting them. This completely eliminated the effect of the ketamine, regardless of the experimenter’s sex. When Georgiou and her colleagues placed a t-shirt worn by a man next to the mice in the fume hood, mice injected with ketamine swam for longer than those injected with a placebo. This suggested that male odour was necessary for the drug to work.

The head of Georgiou’s lab, neuroscientist Todd Gould, learned that antidepressant researcher Ronald Duman at Yale University in New Haven, Connecticut, was seeing similar effects with female researchers in his lab that were working on ketamine experiments. So Gould asked Duman to repeat Georgiou’s swim-test experiment in his own lab. When eight male and eight female researchers injected mice with ketamine, they saw the same results: mice injected by women did not respond to the drug.

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