Depressed rats

A blog post about a cruel, seemingly unnecessary animal model. Compiled from a Twitter thread I did on May 17, 2019. Intended to make you feel uncomfortable. I am so sorry.

Here is the paper (again, NOT endorsed):
Depression Promotes the Onset of Irritable Bowel Syndrome through Unique Dysbiosis in Rats – Takeshi Takajo et al., Gut and Liver 2019; 13(3): 325-332 – DOI: 10.5009/gnl18296

Please file this under animal cruelty. Please do not cite this paper. Please refuse to review papers like these. Please reject papers like these.

This paper is about an animal model that tries to mimic depression. After inducing depression in rats, the researchers found that these animal had a higher chance of getting “irritable bowel syndrome”. How did they induce depression in these rats, you might ask.

=== Animal Cruelty Alert ===

First, rats were put in closed box from which they could not escape. Researchers gave them 60 electrical shocks of 15 seconds each, with intervals of 15 seconds.

Two weeks later, the rats were shocked again for 80 times, but this time in a box with an escape route. Rats were diagnosed with “learned helplessness” if they did not even try to escape, or with PTSD if they escaped a bit more (criteria not well described).

Then, Irritable Bowel Syndrome (IBS) was assessed by inserting a 4 cm long balloon in the rectum of the rats.
Assuming a rat is about 20 cm long, that is 1/5 of their body.
That would be the equivalent of a 20 cm balloon for a human (about 100 cm without legs). That is a HUGE balloon, folks. I am actually getting stomach aches just by thinking about it. Then, the researchers “pressurized” the balloon, and had the rat sit for 30 min. They measured the “colorectal distension”, which appears to be some measure of muscle contraction (I am too afraid to look up ref. 14). Also, note they did this FIVE times per rat.

Then, they looked at the stool microbiome composition. They concluded that the relative abundance of “Clostriales incertae sedis” was lower in depressed rats. But how about the alternative hypothesis that this taxon is killed by electroshocks?

Here is the thing that bothers me the most: There is no need to test the hypothesis using animal experiments. Just take stool samples from humans that are depressed (not a rare disease), and/or count the prevalence of IBS (also not rare) amongst depressed humans.

I am not against animal experiments. They are needed to test hypotheses that we could not ethically test in humans. They have taught us much about e.g. the effect of germ-free development or cancer drugs.

But animal experiments like these are very cruel and not a good representation of human depression. One could do a much better study by taking human stool samples – not invasive, and a very good representation of human depression. There is no point of doing this in rats.

Note that I have called out very similar papers that are trying to “induce” depression or other illnesses in animals by subjecting them to cruel conditions. See for example this Twitter thread from July 2017 or this Retraction Watch post from February 2017.

Let me make this very clear: Electroshocking animals for 60 times is likely to change their microbiomes. That is not a model for (human) depression.
Sticking enormous balloons in a rat’s butt is going to make their gut cringe. That is not a model for irritable bowel syndrome.

After I posted about this on Twitter, I wrote to the editors of this journal to retract this paper – or at a minimum to reflect upon their decision to publish it. I also wrote about this paper in a PubPeer post.

I am (again) pleading to reject gut microbiome manuscripts that involved animal cruelty to mimic a human disease.

I am calling out to animal committees to consider this in their approvals. If there is a good, human, non-invasive alternative, do not approve these types of experiments, please.