5 Times Scientists Gave Animals Drugs (and What They Learned)

[♪ 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]

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