Prozac turns guppies into ‘zombies’


Prozac might need a new warning label: “Caution: This antidepressant may turn fish into zombies.”

Researchers have found that long-term exposure to the drug makes guppies act more alike, wiping out some of the typical behavioral differences that distinguish them. That could be a big problem when the medication—technically named fluoxetine—washes into streams and rivers, potentially making fish populations more vulnerable to predators and other threats.

In recent decades, scientists have uncovered a plethora of ways that pharmaceuticals affect animals in the lab and in the wild, such as by altering courtship, migration, and anxiety. The drugs find their way into the environment through water that pours from sewage treatment plants, which is rarely filtered to remove the chemicals.

But the findings are usually based on an average taken from combining measurements of all the individual animals in a group. Giovanni Polverino, a behavioral ecologist at the University of Western Australia, Perth, and colleagues wondered whether this calculation obscured important but subtle insights about individual animals. Did the drug change behavior similarly in all the creatures in a group? Or were certain kinds of “personalities” affected more strongly?

To find out, Polverino’s team captured 3600 guppies (Poecilia reticulata)—a common silvery fish often used in labs that grows to half the length of an average human’s pinkie—from a creek in northeastern Australia. In the laboratory, the fish and their offspring—as many as six generations—spent 2 years in tanks filled with either freshwater, water with fluoxetine at levels common in the wild, or a higher dose similar to places near sewage outflows.

Then the scientists placed the fish one at a time into a new tank with a white background. In one corner, a dark patch offered a simulated hiding spot, similar to the shade under a rock that the small fish often seek out to avoid predators.

Fish raised in drug-free water displayed a wide range of behaviors. Some darted about, whereas others were much “lazier.” But fish exposed to fluoxetine showed fewer differences; most were moderately active, making them all more like an average fish, the team reports today in the Proceedings of the Royal Society B. The drugged guppies were like zombies who did “not have their individuality anymore,” Polverino says.

All told, there was half as much variation in activity levels among drugged fish, making for a much narrower spectrum of personalities. “It’s an enormous drop [in variability], something I have never seen before,” Polverino says.

Strangely, however, he says not all behavior was affected in the same way. Although the medication appeared to squash individuality when it came to how much the fish swam around, it didn’t reduce variation in how much time individuals spent hiding in the dark spot.

It’s not clear why the hiding behavior wasn’t altered in the same way, Polverino says. One possibility is that hiding from predators is more critical to immediate survival, so that behavior is less sensitive to drug-induced changes.

The discovery could extend to other animals, which have already shown they are sensitive to fluoxetine in the environment. Kathryn Arnold, an ecologist at the University of York, has studied how fluoxetine-laced worms affect starlings, making them less interested in mating—something also seen in humans.

The new findings also show long-term drug exposure can modify behavior, Arnold says. In the past, some scientists have questioned whether behavioral changes seen after brief exposures might fade as animals become accustomed to the drugs. But the new work shows effects persist through multiple generations raised in drug-tainted water.

It’s not clear how the effects seen in the lab would translate to the wild. It could depend on the particular threats confronting a group of fish. Ones that move around more might benefit from finding more food or mates. But they also might run into predators more often, Polverino says. Determining those real-world impacts is now “sort of the $64,000 question,” Arnold says.

Such work is already underway. In Sweden, ecologist Tomas Brodin of the Swedish University of Agricultural Sciences is preparing to study whether an antianxiety drug alters relationships between predatory pikes and the perch and roach they eat. The researcher is implanting a slow-release form of the drug into some of the fish before they are dumped into a lake and tracked. But the Prozac results have prompted Brodin to consider first observing the drugged fish before they are released, to see whether they display any uniform, zombielike behaviors that could skew the results., 9 February 2021