Of all the creatures on earth, octopuses might be the most alien. They could not be more different from us, with powerful tentacles, three hearts, blue blood, and neurons spread throughout their entire body. These strange creatures have inspired fear through history, such as the myth of the Kraken. More recently, they have been recognized as incredibly intelligent, famed for their problem solving and escapist tendencies. It was these cognitive capabilities that led scientists to use octopuses as a model organism to study the evolution of the nervous system and how intelligence evolves in a branch that split from ours over 500 million years ago.

The California two-spot octopus (Octopoda bimaculoides is the most commonly used in scientific research. They are relatively easy to care for and only live to up to 2 years old, which is around the lifespan of laboratory rats. Unlike lab rats, however, octopuses are notoriously solitary creatures. Most species spend their whole lives without interacting with another octopus, coming together at the very end to mate, nurture their eggs, and then die. It was then very surprising when one group of scientists discovered that they could turn octopuses social.

In a notable 2018 study, researchers interested in the evolution of social behavior turned to octopuses as their model. They started with the serotonin system. Serotonin is an ancient molecule used by almost every living thing, from fungi and plants to insects and mammals. Neurons and other cells pass the molecule back and forth to signal everything from movement to learning. In many animals, serotonin plays a major role in social behavior. The researchers found genetic orthologues for the human serotonin transporter gene in octopuses. However, it was unknown if serotonin played a role in social behavior in octopuses. The question was: how ancient is the social component of this neurotransmitter?

To investigate the social side of serotonin, researchers turned to party drug. MDMA, commonly known as ecstasy, E, or Molly, is a drug that targets the serotonin system. The drug blocks the serotonin reuptake transporter, a receptor that removes serotonin from the synapse, which results in serotonin flooding the brain. As a result, people experience altered sensory perception, higher energy, and increased sociality, alongside negative health effects common to drugs of abuse. MDMA is commonly used at parties and raves because of its prosocial effects. It makes people feel more connected, empathetic, and extroverted. This made researchers wonder: what would it do to octopuses, a notoriously asocial animal?

To test this question, they had to first figure out how to study social behavior in octopuses. They adapted a behavior task commonly used in rodents, the three chambered social approach assay. In this task, the octopus being tested was placed in an aquarium with three chambers. The middle chamber was empty. One of the chambers on either side contained a novel male or female octopus (social object) restrained by a plastic basket. The other chamber had a novel object– a toy Star Wars figurine.

Three chambered social approach assay used by the researchers. Figure created with BioRender.com.

The researchers then put the test octopus in the middle chamber and measured how much time they spent in the chambers with the toy and the other octopus. When the other octopus was a male, the test subjects spent more time with the toy than with the other octopus or the empty chamber. However, when the other animal was a female, they spent more time with the octopus than with the toy.

After measuring the baseline social interactions, the researchers set out to test how MDMA would affect social behavior. They decided to use only male octopuses as the social object due to their aversive effect in the baseline tests. Since octopuses don’t prefer interacting with males, the evidence would be much stronger if the drug made them do so.

They did two rounds of the social interaction test, first without the drug and then after placing the animals in a water bath with MDMA. The results were stark: the animals spend more time with their fellow octopuses after the drug.

In addition, the quality of these interactions changed. Dr. Gül Dölen, the co-author of the study, described the octopuses as “essentially hugging,” after MDMA. They were using more of their body, even exposing their sensitive ventral underside where their beaks are located.

Although this paper is preliminary and has some experimental flaws, its ideas are far-reaching. It demonstrates that serotonin is an evolutionary throughline. One small molecule that connects us so profoundly to other humans also connects us back 500 millions years to a species so strange that a group of scientists once speculated that octopuses are aliens.

At a fundamental level, human and octopus brains are more similar than would be expected, which suggests that certain ideas in neuroscience of “more evolved” and “less evolved” regions of the brain might not be accurate. Dr. Gölen commented, “What we’re arguing is that the brain regions don’t matter. What matters is that they have the molecules, the neurotransmitters, and some configuration of neurons. They have the serotonin transporter, and that’s enough.” Octopuses are living proof that there are more evolutionary paths to both intelligence and social behavior than we once thought.

Peer edited by Nila Pazhayim

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