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It might seem like researchers give animals drugs just to make a good headline, but these experiments have taught scientists a lot.

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Sources:

MDMA
https://www.nytimes.com/2018/09/20/science/octopus-ecstasy-mdma.html
https://www.cell.com/current-biology/fulltext/S0960-9822(18)30991-6
https://www.drugabuse.gov/publications/research-reports/mdma-ecstasy-abuse/what-mdma
https://www.telegraph.co.uk/news/newstopics/howaboutthat/3328480/Otto-the-octopus-wrecks-havoc.html

Cocaine
https://www.nytimes.com/2009/01/06/science/06bees.html
http://jeb.biologists.org/content/212/2/163.short
https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC47626/?page=1

Alcohol
http://science.sciencemag.org/content/335/6074/1351
https://www.sciencemag.org/news/2012/03/sexually-rejected-flies-turn-booze
https://onlinelibrary.wiley.com/doi/abs/10.1002/syn.10226

Opioids
https://www.sciencedirect.com/science/article/pii/S0028390818303289
https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis
https://cen.acs.org/articles/96/i8/Vaccines-against-addictive-drugs-push.html

Psilocybin
https://link.springer.com/article/10.1007/S00221-013-3579-0
https://www.sciencedirect.com/science/article/pii/B978012800212400073X
https://www.livescience.com/37914-psilocybin-eliminates-traumatic-memories.html

Images:
https://www.videoblocks.com/video/boxer-dog-wiggling-tail-with-excitement-while-being-approached-c8o9yem
https://www.videoblocks.com/video/a-funny-cat-wearing-a-santa-claus-hat-playing-a-keyboard-or-organ-rnf9iylqmjbuy94zm
https://en.wikipedia.org/wiki/File:CaliforniaTwoSpotOctopus1.jpg
http://www.thinkstockphotos.com/image/stock-illustration-star-wars-vector-pack/1014351826
https://en.wikipedia.org/wiki/File:Honey_Bee_takes_Nectar.JPG
https://commons.wikimedia.org/wiki/File:Erythroxylum_novogranatense_var._Novogranatense_(retouched).jpg
https://www.videoblocks.com/video/bees-work-on-honeycomb-with-honey-some-cells-already-closed-rnxlvimifirm769gn
https://en.wikipedia.org/wiki/File:Drosophila_melanogaster_Proboscis.jpg
http://www.thinkstockphotos.com/image/stock-photo-pet-rat/492486990
http://www.thinkstockphotos.com/image/stock-photo-albino-mouse-playing/480517277
https://en.wikipedia.org/wiki/File:Psilocybe_semilanceata_6514.jpg
[♪ INTRO] “Scientists get spiders high on weed!” “Watch what happened when a scientist gave this octopus ecstasy!” Over the years, you might have seen some headlines like these.

This kind of research makes for great click-bait-ey articles, because it creates a ridiculous picture in our minds, and humans love to watch animals being silly. After all, the whole point of the internet is to spread funny cat videos, right?

But scientists don't do these experiments just to have good stories to tell at parties. They do them to learn more about how the brain and nervous system works, and to study the effects of these drugs in a safer, more controlled way. So, here are five times scientists gave animals drugs, and what they actually learned.

Normally, octopuses don’t really like to hang out with friends. Aside from a brief get together for mating, they’re pretty much loners. So to learn more about their social behavior, scientists recently decided to see what happened if they gave them ecstasy.

Yes, that ecstacy. The scientific term for ecstasy is MDMA, which stands for a really long chemical name that we’ll just put up on the screen for you. It’s both a stimulant and a hallucinogen, and it’s also known to make people more empathetic.

It does this by interfering with the neurotransmitter serotonin, which, among other things, regulates specific social behaviors. Ecstasy causes an excess of serotonin to build-up in the gaps, or the synapses, between brain cells. Ecstasy’s effects on social behaviors are well-documented in humans, but the researchers wanted to see if this happened in octopuses, too.

In the experiment, published in 2018 in Current Biology, researchers rounded up some young California Two-Spot Octopuses. They gave some MDMA and others a placebo. Then, they gave them a choice: They could either hang out with a Star Wars figurine,.

Chewbacca or a Stormtrooper, for the record, or hang with another octopus. The animals high on ecstasy chose to hang out with a fellow octopus more often, even hugging the enclosure their new friend was in. Meanwhile, control octopuses usually wanted to play solo with Chewie.

When the researchers took a close look at the octopus genome, they found that octopuses and humans have a very similar gene for the serotonin transporter protein, which helps regulate the amount of serotonin in the synapses. That’s most likely why the ecstasy had a similar effect on the octopuses as it does on humans. Because the common ancestors of octopuses and humans went their separate ways more than 500 million years ago, this suggests serotonin has been playing a role in social behaviors for a very long time.

Honey bees already seem pretty buzzed as they zip from flower to flower. But a few years ago, scientists decided to give them some cocaine. They were trying to untangle why cocaine seems to do different things in humans and insects.

In humans, the drug causes a buildup of the neurotransmitter dopamine, which plays a big role in the reward pathway. This pathway is a network in your brain that makes you feel good when you do something necessary for survival and reproduction. So having excess dopamine floating around makes you feel really, really good, but also too good.

Cocaine makes people euphoric, energetic, hypersensitive, and super enthusiastic. But because it tricks the reward pathway, it makes them want to take the drug again and again, leading to addiction. In insects, though, things seemed to be pretty different.

See, cocaine is actually made by the coca plant to prevent insects from eating it. It’s a sort of natural insecticide, where caterpillars eating cocaine-laced leaves lose motor control and stumble off the plant. For a while, most scientists assumed that the rewarding effect cocaine has on humans just didn’t happen in insects.

But in 2009, in a study published in the Journal of Experimental Biology, researchers decided to officially test that assumption using honey bees. Certain honey bees tell their hive mates the location and quality of flower resources by dancing. And when the researchers gave the bees low doses of cocaine, they over-exaggerated the quality of the resources they had found.

Kind of like how a person on the drug would get, like, really enthusiastic. When the bees were cut off from the cocaine, they even went through withdrawal symptoms, performing poorly on memory and learning tasks. Yes, we can give memory and learning tasks to bees.

That suggested our ideas about how cocaine affects insects might have been wrong. At least based on this experiment, it seemed like those rewarding effects happened after all. Still, it’s not like coca plants make insects addicted, so there had to be something else going on, too.

The scientists suggested that the motor effects cocaine causes are still important in driving insects away, and that the rewarding effects in honey bees are kind of a side effect. Then, if an insect does come back for more leaves, it likely gets so much cocaine that it overdoses and dies, which is why all of the coca plants in the world haven’t already been devoured. At some point, you might have heard of somebody trying to “drown their sorrows”.

This is the idea of someone trying to get over something disappointing by drinking alcohol. Among other things, alcohol causes the release of our old friend dopamine, and since that causes happy feelings, that presumably helps someone feel better about their day. The thing is, though, the desire to drown your sorrows might not just be a social convention, at least, according to one 2012 experiment with fruit flies.

In the experiment, which was published in the journal Science, scientists divided 24 male fruit flies into two groups. Half were put into vials full of females who wanted to mate. And the males seemed happy to oblige.

The other half were put into separate vials with a female fly that had just mated and was not interested in mating again. These males were rejected. Then, the scientists offered both groups of males some mashed food mixed with alcohol.

Like in humans, alcohol activates the reward pathway in fruit flies, so the scientists expected all of the males to opt for it, but that is not what happened. Instead, mated males seemed to have an aversion to the alcohol, while the rejected ones preferred it. In fact, they drank an average of four times as much as their mated counterparts.

Even more surprisingly, there may have been a neurological reason for that. After follow-up observations, the scientists discovered that the rejected flies’ brains had about half as much of a chemical called neuropeptide F, which plays a role in alcohol preference. And if researchers experimentally decreased the activity of neuropeptide in the mated males’ brains, they saw them drink like the rejected males and vice versa.

The scientists suggested that the drop in neuropeptide F was a signal for the fruit flies to do something that would trigger their reward pathway. And in this case, that meant drinking alcohol. The research is important because humans actually have our own version of neuropeptide F.

It’s called neuropeptide Y, and folks with depression and post-traumatic stress disorder often have lower levels of it. There’s also some evidence in rats that it plays a role in alcohol addiction. Right now, these fruit fly results don’t translate to humans.

But if future experiments show similar results in people, it could help us develop new treatments for alcohol abuse. If you’ve watched any news in the last few years, you’ve probably heard about the opioid crisis. Opioids are drugs used to treat pain.

They include prescription drugs like codeine and morphine, along with street drugs like heroin. They work by binding to certain receptors in the brain and spinal cord and blunting pain signals, and they are extremely effective. These drugs are often prescribed after major surgeries, but when used incorrectly, they can be addictive.

That’s because they also tap into the brain’s reward pathway and increase dopamine release. Opioid abusers can develop a tolerance for the drug, requiring larger and larger doses to get the same effect. And in the United States, that leads an average of 115 people overdosing on them every day.

Scientists at the Scripps Research Institute wondered if there might be a way to vaccinate someone against addiction. And in 2018, they published a paper in the journal Neuropharmacology where they explored this idea by developing and testing an opioid vaccine on rats. Normally, the body doesn’t have an immune reaction to opioids.

So to make the rats’ immune systems recognize one, in this case, oxycodone, as harmful, they attached the drug molecule to a large protein. In this experiment, they used a portion of the tetanus toxoid protein. The hope was that, when the rats were injected with this oxycodone vaccine, they would make antibodies that recognized the oxycodone.

Then, the next time the rat got a dose of the regular drug, antibodies would attach to the drug molecule. And that would make them too big to get into the brain and release dopamine. The cool thing is, it sort of worked!

In follow-up experiments, the researchers gave rats the option to self-inject oxycodone through an IV by pressing a lever in their cage. They found that all of the unvaccinated rats had developed an addiction, but only about half of the vaccinated rats did. And the rats in that half more easily kicked the oxycodone habit when the researchers made it harder to self-inject.

Now, addiction behavior in humans is a lot more complicated than rodents in a controlled laboratory. But experiments like this are helping scientists work out the kinks in making a human vaccine. If scientists can get these treatments to work in humans, a person in recovery could be vaccinated against the drug they abused.

That way, if they had a relapse, the drug wouldn’t get them high. And in combination with other therapies, like counseling, that might be game-changing. Finally, scientists sometimes get animals high to see if drugs can be used in a helpful, rather than a harmful way.

One of those experiments happened in 2013, when scientists gave mice ‘shrooms. Or more specifically, the active ingredient in magic mushrooms: psilocybin. Psilocybin is most famous for causing hallucinations, but it also binds to serotonin receptors.

And besides regulating social behavior, like in the octopuses, serotonin is also involved in short-term memory formation and in the growth of new brain cells. In this study, published in Experimental Brain Research, scientists wanted to see what effect the drug had on scary memories, and if it played a role in fear conditioning, essentially, training an animal to be afraid of something. First, they split the mice into groups: some who received various doses of psilocybin, and others who received harmless saline injections.

Then, they played a tone and gave the mice a painful shock. They did this repeatedly until the mice froze in fear every time they heard the sound. Next, the team looked at how long it took to undo this fearful behavior.

They started by playing the tone but not shocking the mice afterwards. And they recorded how many times they had to do this before the mice stopped freezing. Mice that received low doses of the psilocybin lost their fear of the tone faster than mice that got high doses or mice that got saline.

The low dose mice also grew more new brain cells. The researchers don’t think these low doses were enough to make the mice hallucinate, either. But, like you might imagine, they did admit it’s a little hard to tell whether a mouse is hallucinating.

Scientists are hoping that someday they might be able to strategically use drugs like psilocybin to help treat conditions like post-traumatic stress disorder. In the future, a doctor might be able to give a patient a small dose of it during something like exposure therapy, where you face your fears, to help patients overcome them. We’re not quite there yet, but this research is definitely a good start.

While some of these experiments might seem silly at first glance, they've taught scientists a lot. They’re helping them learn how drugs affect the brain, how we might use them clinically to treat psychiatric conditions, and how we might better help people that become addicted to them. So for as good as all the headlines are, the research is pretty solid, too.

Another place you can hear about some solid research is SciShow Tangents, our new weekly podcast, produced in collaboration with WNYC studios. Each week four of the people who work on the SciShow YouTube channels, including me, pick a theme and try to one-up each other with all the cool science facts and research that we find based on that theme. The show has different segments, like one where someone presents a true fact alongside two fake facts, and everyone else has to untangle the web of lies to figure out which one is true.

We usually end up going on a bunch of tangents, hence the name of the podcast, and we try to end every episode with a fact about butts. It’s a real good time! It’s called SciShow Tangents and you can check it out wherever you get your podcasts! [♪ OUTRO].