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Giving DOI to zebrafish: A look at the Duke researchers testing how psychedelics affect the brain

November 13, 2023 | By Winston Qian
Originally published by Duke Chronicle


Duke researchers are studying the brain by giving psychedelics to larval zebrafish.

As a “side project” in the Naumann Lab, neurobiology doctoral student Minel Arinel, alongside senior Aloye Oshotse and junior Elysia Ye, is observing the physiological shifts and behavior of larval zebrafish after receiving doses of 2,5-Dimethoxy-4-iodoamphetamine (DOI), a substance with hallucinogenic effects similar to lysergic acid diethylamide (LSD). 

“[A] challenge is talking to people and saying, ‘We give fish psychedelics and then look at the responses,’” Arinel said. “They ask, ‘Why? Why are you giving tiny little fish larvae psychedelics? What's the point?’”

Through these experiments, Arinel hopes to uncover how psychedelics impact various biomarkers and behaviors. While other studies experiment on the effects of psychedelics on psychiatric diseases, Arinel believes that more work needs to be directed toward understanding how these substances affect the body.

While it is an unusual decision to give tiny fish larvae psychedelic substances, Arinel states that they are actually useful models for observation, due to their small size and translucent body. 

“We can use the larval zebrafish as a model to understand neural circuits across the entire brain,” she said. “Being able to look at an entire organism and how it changes all the bodily functions like heartbeat, gut motility and all of that … that’s really valuable.” 

At the same time, researchers possess previous knowledge about behavioral patterns in zebrafish, which can be used as a baseline to observe changes caused by DOI. According to Arinel, zebrafish are “very visual animals” that dedicate half of their brain to visual processing and how zebrafish convert visual stimuli into motor outputs.

Results from the study

Researchers observed that zebrafish dosed with low concentrations of DOI showed much movement and exploratory behavior, even in dark conditions. 

“I think of it as if you're tripping, and all of a sudden the lights go out, your mind would probably imagine a lot of hallucinations, and maybe it will induce some exploratory behavior,” Arinel said. 

Arinel attributed the behavior as likely resulting from the zebrafish exhibiting higher visual sensitivity, thus affecting their motor functions.

While zebrafish moved more with low concentrations of DOI, the movement and visual sensitivity of the zebrafish started decreasing as the team increased the DOI dosage.

“They just stopped responding and started floating around,” Arinel said. “... This is also similar to where if you take too high of a dose of a drug, all of a sudden you just want to sit down, go into a corner and then just wait for it to go away.” 

Future steps for the study

To explain these observations, the team plans to use brain imaging to analyze the responses of various brain regions to DOI. At the same time, the team looks to understand how interactions between these brain regions shift due to psychedelics. 

“Our main future direction is to use a recurrent neural network model to predict how the functional connectivity between brain regions change before and after exposure to DOI,” Arinel said.

Although this study is not a clinical study performed on humans and will likely not directly translate to humans, Arinel believes that it is a step closer to understanding diseases and treatments in the fields of psychiatry and neurobiology. 

Arinel referred to when someone contacted her about his 14-year-old son who has akinetopsia, a condition which makes it difficult to perceive motion. 

Research from that son’s father showed “anecdotal evidence” that psychedelics could cause visual processing effects similar to the symptoms of akinetopsia. He connected with Arinel in hopes of looking into a possible relationship between the study’s findings and his son’s case. 

“Whatever we find is not going to directly translate to such diseases like akinetopsia, for example,” Arinel said. “But maybe we can provide some basic science understanding, some mechanistic understanding of what is going on.”