Fish Out Of Water, On Ketamine

By Neuroskeptic | August 23, 2010 12:38 pm

Ketamine is a drug of many talents. Used medically as an anesthetic in animals and, sometimes, in humans, it’s also become widely used recreationally despite, or perhaps because of, its reputation as a “horse tranquilizer”.

Ketamine’s also a hot topic in research at the moment for two reasons: it’s considered an interesting way of provoking the symptoms of schizophrenia, and it’s also shown promise as a fast-acting antidepressant.

Anyway, most ketamine research to date has been done in either humans or in rodents, but New York pharmacologists Zakhary et al decided to see what it does to fish. So they put some ketamine in the fishes water and saw what happened: A Behavioral and Molecular Analysis of Ketamine in Zebrafish.

A high dose, 0.8%, just made the fish unconscious. Well, it is an anesthetic. But a low dose (0.2%) had rather more complex effects. It sent them literally loopy – they started swimming around and around in circles, usually in a clockwise direction. Control zebrafish swam about and explored their tanks without any circling behaviours.

They also examined the effect of ketamine on the “hypoxic stress” response, i.e. what happens when you take the fish out of water (only for 20 seconds, so it doesn’t cause any real harm.) Normal fish struggle and gasp for water in this situation, unsurprisingly. Ketamine strongly inhibited this.

So what? Well, it’s hard to say what this might mean. It would be great if the zebrafish turned out to be a useful experimental model for investigating the effects of ketamine and similar drugs, because they’re much easier to work with than rodents (for one thing, it’s a lot easier to just put a drug in a fish tank than to inject it into a mouse.)

However, it remains to be seen whether swimming in circles is a useful analog of the human effects of ketamine. Ketamine can make people act in some pretty stupid ways, but walking around in little circles is extreme even by K-head standards…

Link: I’ve blogged about ketamine before: I’m On K, You’re On K.

ResearchBlogging.orgZakhary SM, Ayubcha D, Ansari F, Kamran K, Karim M, Leheste JR, Horowitz JM, & Torres G (2010). A behavioral and molecular analysis of ketamine in zebrafish. Synapse (New York, N.Y.) PMID: 20623473

  • Art

    Here is another recent paper about ketamine in rats. It suggests that the antidepressant action of ketamine involves synaptogenesis.

    By the way, the study linked in the blog about ketamine/bipolar says it's “double blind”. Ketamine is a powerful hallucinogenic, so how can it be blind? Why isn't it considered a fatal flaw for this kind of research?

  • Anonymous

    Years ago in dark days I was a intense drug addict. My pattern would be to alternate for periods of days or weeks between ketamine and heroin. Both of which have opiod and disassociative properties. The shared affinity of ketamine and opiates was very obvious. If I had been on K the day before and even though long worn off the injection of an opiate would result in a opiate high *and* an instant and very pronounced feeling of being on ketamine, much above and beyond the (relativly mild) disassociative effect of heroin. Similarly, ketamine is one of the very few things that mitigates opiate withdrawal and is not classified as an opiate. My withdrawals were severe, as I used to react synth of asprin kits with morphine tablets for what would colloquially be refered to as “primo stuff”, and lots of it.

    Having been quite involved with ketamine I can confidently say that the majority of $ spent on it is by people who are classically addicted, as much to the dissasociation as to the quasi-opiate like effects.

  • Anonymous

    Sorry, meant to also add that if ketamine is an antidepressant it's probally a similar effect as low-dose bupie? lol.. bupie as an antidepresant. Why not just use low-dose cocaine??

    – matt

  • Zarathustra

    As the saying goes, only fools and horses (and zebrafish) take ketamine.

    Last time I saw someone on K she was panicking because she believed her teeth were falling out. And this stuff is enjoyable, is it?

  • Anonymous

    Zarathustra, it is not enjoyable, it is a temporary oblivion with rough edges. Do you think anybody actually enjoys a cigarette the first time they smoke?? Yet so many smokers.

  • veri

    lol, kinky ketamine.. sounds hot. I need to be tranquilized.. please sir, I can't live like this no more, gimmi gimmi kleidoscope kangaroo.

  • Neuroskeptic

    Naughty people have been known to fake ADHD in order to get Ritalin, pain in order to get opiates, etc. I wonder if anyone's ever pretended to be an agitated horse in order to get ketamine? Actually, maybe it would take two people.

  • veri

    My first cigar was natural. Like I was born embodying the temple of an opiate factory. It was wrinkle consciousness that made me quit. So no doubt this horse chattering molars are an uber awesome yeah! for some.

  • veri

    lol! agitated horse! love it!

  • Anonymous

    I don't know why everyone likes to smear ketamine as a horse tranquillizer. If everyone knew that its main medical use is as a paediatric anaesthetic, they might not have such a ridiculous opinion of its effects. “Horse tranquillizer” makes one imagine taking it will just knock you out, which is very far from the truth, which is that it can be a very interesting psychedelic experience.

  • Neuroskeptic

    Well it's like anything else, mud sticks. Once you get a reputation as a horse tranquilizer, it's impossible to shake.

    It's like how no-one will ever be able to think of Tiger Woods as a golfer again. He's stuck as a philanderer for ever.

  • Henry Buckfist

    Interestingly, Echo the Dolphin was created by a man who regularly put himself in an isolation chamber (egg-water) on Ketamine.

    Reading this and seeing the Image of the Fish in circles made my night. This is entirely my experience.

    Peace be with you, and all fishes in the bodiless sea consciousness!



No brain. No gain.

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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