April 25, 2012 | 2
It’s day 4 of the Experimental Biology meeting, and I looked at a poster using zebrafish as a model for behavioral effects of hallucinogens, but there was also a great symposium on treatments for affective disorders, as well as great posters on stress, serotonin systems, and more. But we’ll stick with the zebrafish for now.
When most scientists think of how we might study drug response, we usually think of rats or monkeys or mice, pressing levers to deliver drug, or showing different behaviors in response to treatments. Sometimes we will see studies on flies (http://arstechnica.com/science/news/2012/03/a-lack-of-sex-drives-flies-to-drink.ars). But what about fish? Specifically, zebrafish?
Zebrafish are a pretty attractive model for scientific research. They have a completely sequenced genome, a series of easily observed and modified behaviors, and they are cheap(er) than rodent or primate models. And it’s easy enough to test the effects of different drugs: just pour some into the tank and watch what happens, a much less stressful form of administration than having to inject a mammal.
There are already studies out there in zebrafish using cocaine (http://www.ncbi.nlm.nih.gov/pubmed/18499199) and morphine (http://www.ncbi.nlm.nih.gov/pubmed/22205946). Allan Kalueff’s lab at Tulane University is interested in hallucinogens, drugs like that mescaline and psilocybin. In particular they looked at mescaline, a drug derived from the peyote cactus, psilocybin, a drug derived from mushrooms, and phencyclidine (PCP), a drug that was once developed as an anesthetic, but has powerful hallucinogenic properties. Mescaline and psilocybin act at receptors for the neurotransmitter serotonin (http://scientopia.org/blogs/scicurious/2010/08/25/back-to-basics-3-depression-post-4-the-serotonin-system/), and PCP has its mechanism of action via the glutamate system (http://en.wikipedia.org/wiki/Phencyclidine). All three of them are powerful hallucinogenic drugs. And while you can’t tell if a zebrafish is seeing things, their easily classified behaviors can be used to examine similarities and differences between drugs, and help to understand their mechanisms of action.
So Collins, a student in Kalueff’s laboratory, has given zebrafish various doses of hallucinogens, and looked at how the fish behave. He started with the novel tank test, where you put a single fish in a novel tank with drug or saline. When the fish are exposed to a novel tank, they immediately swim to the bottom, and start to swim to the post as they get more comfortable, a measure of anxiety-like behavior. But with PCP or mescaline, the fish swam to the top of the tank more quickly than control fish, suggesting that they had decreased anxiety. Fish on PCP also showed more erratic swimming behavior. Collins also looked at social behavior in the shoaling test. Zebrafish are social, and like to shoal together, but will show differences in social behavior in response to different drugs. When Collins gave the fish mescaline, the fish appeared to be more social, showing decreases in inter-fish distance. Psilocybin and PCP also produced increases in the stress hormone cortisol.
By looking at the effects of hallucinogenic drugs in fish behaviors , Kalueff’s lab hopes to use the zebrafish as a model to understand the mechanisms behind drug-induced behaviors, and help us to understand how these very complicated drugs have their effects. Not only that, hallucinogenic drugs are often used to model psychiatric disorders like schizophrenia. So some day, zebrafish on PCP might provide the key to some complicated disorders.