By Philip  |  11-22-2017   News
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Recent experiments on the effectiveness of ketamine in the rodent model of depression revealed some rather curious findings. The studies results, presented at the November 14 meeting of the Society for Neuroscience (SfN) in Washington DC corroborated some previous studies that suggested ketamine may be a useful aid against treatment-resistant depression, with a bit of a twist. The results initially seemed dependent on the sex of the researcher performing the injection.

The <a href="http://www.theplasticscreen.com/ketamine-clinics-show-promise-for-treatment-resistant-depression/">use of ketamine as an experimental treatment for depression</a> is becoming more mainstream. There are <a href="https://www.inquisitr.com/4339939/ketamine-clinics-show-promise-for-treatment-resistant-depression/">less than ten states in the USA that do not have at least one legal ketamine clinic</a>. Ketamine is still occasionally used as an anesthetic drug in humans and animals but is also a well-known club drug. The recent findings regarding this ketamine research on rodents raise important questions about reliability and replicability of rodent experiments.

<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">More questions about the reproducibility of behavioural experiments in mice: ketamine lifts rodents&#39; mood only if administered by male researchers. Scent of scientific success? <a href="https://t.co/0aNG2ofcCY">https://t.co/0aNG2ofcCY</a></p>&mdash; Roger Highfield (@RogerHighfield) <a href="https://twitter.com/RogerHighfield/status/931804668900102144?ref_src=twsrc%5Etfw">November 18, 2017</a></blockquote>

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After Polymnia Georgiou found that she was not able to replicate a colleague's results in a forced swim test, researchers trained their attention on possible reasons why. One theory was that it was scent related. To test the hypothesis, a fume hood was used to block any scent of the researchers. Oddly enough, regardless of sex, ketamine was not effective when the scent factor was removed. This <a href="http://www.nature.com/news/sex-matters-in-experiments-on-party-drug-in-mice-1.23022?error=cookies_not_supported&code=19ac118c-ed75-4212-875a-9f345becc926">implicated the scent of the male researchers as a possible mechanism in the efficacy of ketamine</a>.

Todd Gould, the head of Georgiou's lab, later found that Ronald Duman, antidepressant researcher at Yale University, had found a similar circumstance when eight male and eight female researchers applied ketamine to test antidepressant potential of ketamine. Once again, the mice injected by women did not respond. Georgiou and her team experimented with other antidepressants and didn't have the same effects, so it seemed as if there was a specific interaction between male scent and the effects of the ketamine in the rodent brain.

This was not an isolated case, however. A <a href="https://www.nature.com/articles/nmeth.2935.epdf>2014 paper in Nature Methods also reported mice being more stressed but less sensitive to pain</a> when exposed to olfactory exposure to males. Silvana Chiavegatto of the University of São Paulo in Brazil noted the same phenomenon studying depression in rats, without ketamine being introduced as a factor. If this situation occurs in multiple cases in the rodent model of the brain, it could cross over to other types of trials involving rodents or even some other mammals.

<blockquote>“I think it’s really fascinating, with wide implications for our field,” says Adrienne Betz, a behavioral neuroscientist at Quinnipiac University in Hamden, Connecticut. But she cautions that the results are preliminary, and it remains to be seen whether the effect is specific to ketamine and to mice.</blockquote>

Not everyone disagrees with the sex-based scent theory. Hundreds of papers regarding female experimenters demonstrate the effectiveness of antidepressants, including ketamine, in rodents even with female researchers. Some other factors possibly involved may be whether researcher is stressed when the mouse or rat is injected.

<blockquote class="twitter-tweet" data-lang="en"><p lang="en" dir="ltr">Ketamine Clinics Show Promise For Treatment-Resistant Depression - The Inquisitr <a href="https://t.co/chaG1jAAb0">https://t.co/chaG1jAAb0</a></p>&mdash; Mental Health (@mentalhealing) <a href="https://twitter.com/mentalhealing/status/881581214649511937?ref_src=twsrc%5Etfw">July 2, 2017</a></blockquote>

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Ketamine has been highly effective in humans, even in treatment-resistant models of depression, and Gould doubts that sex of the administrator in humans would affect how well it works, though this has not been tested. As is, rather than invalidating previous studies, it raises interesting questions as it casts much of rodent and animal trial research in a possible new light

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