Ecstasy: another link

connecting human and

octopus brain chemistry
According to the study, “A Conserved Role for Serotonergic Neurotransmission
in Mediating Social Behavior in Octopus”, octopus, like humans, experience a
greater fondness for social interactions under the effects of ecstasy or MDMA
(Edsinger and Dölen, 2018). This commonality could be due to an orthologous
gene, SLC6A4, that codes for the sixth trans-membrane domain (TM6) of the
serotonin transporter (SERT). It is known today that octopuses and humans
evolved from a distant ancestor, but the parallel SLC6A4 gene reveals the
preservation of genetic information shared since that branching event hundreds
of millions of years ago.
 Although humans and octopuses share minimal similarities in physical appearance, on a

molecular level, it is fascinating how much of our genetic code is orthologous. In this study,

researchers Edsinger and Dölen seek to investigate the relatedness of the SLC6A4 gene between

humans and octopuses by testing the functionality of SERT in response to MDMA. The

researchers did not state their hypothesis explicitly, but the discussion of their results suggested

that they anticipated SERT in octopuses to behave similarly to that of humans where the effects

of MDMA increase friendly social interactions. This hypothesis is backed by whole-genome

sequencing done in previous studies that revealed 100% identity alignment of octopus and

human SLC6A4.

To study SERT functionality, the researchers decided to compare how octopuses

approached a social object that is “normally aversive” prior to and under the influence of

MDMA. Individual California two-spot octopuses (Octopus bimaculoides) were placed in a

three-chambered tank with partitions of that center chamber opening into an object-chamber

containing a novel toy and a social-chamber containing a male octopus of the same species

(Figure A). Then, the researchers timed how much time was spent in each chamber for thirty

minutes prior to and after the subject was placed in an MDMA bath for ten minutes (Figure B).

The results are gathered in line graphs color-coded by chamber and separated into data points for

each of the four individuals (Figures D-J) and as a collective (Figures E-K). If the researchers’

hypothesis was correct, then the graphs would show a significant time increase in the social-

chamber after the administration of MDMA compared to before (Figure L). On the other hand, if

no difference was observed and the data collected is unlikely due to chance, then the hypothesis

is rejected (Figure M).

 The actual results matched with the trend expected if the hypothesis was correct showing

an increase in time spent in the social chamber and time elsewhere decreasing or staying the

same during post-trial (Figures D-K). These results support the theory that MDMA increases

social interactions in octopuses due to an influx of the feel-good molecule serotonin attributed to

the intact functionality of SERT. We can further infer that the similarity in SERT function is

because of the same SLC6A4 gene in humans, inherited by both species from a common ancestor

long ago. The conservation of this gene over countless generations is remarkable and how this

small piece of genetic information has managed to remain unchanged in both species is an

interesting avenue for further research. Perhaps investigating the evolutionary advantages of

SLC6A4 and calculating mutation rates could shed more light on why a change has not occurred

in that coding region.

This study was highlighted in an article from Science magazine titled “Like Humans,

Octopuses Want More Hugs When High on Ecstasy” (Schembri, 2018). Overall, I thought

Schembri’s reporting of the study was accurate, concise, and enjoyable to read especially to

those without a background in science. With that said, after reading the entire study, it became

apparent that Schembri left out a lot of details for the sake of simplicity. The actual MDMA trial

was only a portion of the overall study. Edsinger and Dölen also compiled whole-genome

sequencing data for not just humans and octopuses, but also for other species expected to inherit

the SLC6A4 gene. The researchers also ran a test session to observe the natural social behavior of

octopuses under the same conditions of the three-chambered tanks (Figure C). Nonetheless,

Schembri’s delivery was to the point and retained the integrity of this study. It did not muffle the

reader with facts and acted as guidance for navigating the dense scientific paper.
Figure A: Experimental setup of the three chambers.
Figure B: Timeline of the different parts of the experiment.
Figure C: Results from test session to see how much time the subject octopus spent in each
chamber when the subject chamber housed a male versus a female octopus. Results indicated
that the subject octopuses spent less time in the social chamber when a male octopus is present.
Therefore, that became the setup for the experimental trials as the “normally aversive” social
interaction.
Figure D-J: Each line represents an individual subject. The lines show how much time was spent
in each of the chambers (and during transitions). Lines with positive slopes indicate that time
spent increased post-trial and the opposite is true for negative slopes.
Figure E-K: The results from each subject were combined to show an overall trend of time spent
in each chamber pre and post-trial. Only the trend for the social chamber proved to be significant
with a p-value of 0.0274. The other trends all had p-values greater than 0.1 rendering them
statistically non-significant.

L Hypothesis was Correct M Hypothesis was Incorrect

1800 1800
Time (s) spent in the Social

1600

Time (s) spent in the Social

1600
1400 1400
1200 1200
Chamber

Chamber
1000 1000
800 800
600 600
400 400
200 200
0 0
Pretrial Posttrial Pretrial Posttrial

Figure L: If the hypothesis is correct and MDMA increases social interactions in octopuses, then
time spent in the social chamber should increase after the octopus is under the effects of MDMA.

Figure M: If the hypothesis is incorrect and MDMA has no effect on social interaction in
octopuses, then time spent in the social chamber would not change significantly after the octopus
is under the effects of MDMA.
References

Edsinger, Eric, and Gül Dölen. “A Conserved Role for Serotonergic Neurotransmission in

Mediating Social Behavior in Octopus.” Current Biology, 2018,

doi:10.1016/j.cub.2018.07.061.

Schembri, Frankie. “Like Humans, Octopuses Want More Hugs When High on

Ecstasy.” Science | AAAS, American Association for the Advancement of Science, 20

Sept. 2018, www.sciencemag.org/news/2018/09/humans-octopuses-want-more-hugs-

when-high-ecstasy.