BioEd Online

Minute amounts of an anti-anxiety medication found in river water could make fish bolder, antisocial, and voracious, researchers have found.

The drug, oxazepam, is among the most heavily prescribed psychotherapeutic drugs, and is thought to be highly stable in freshwater environments. It acts by binding to receptors in the brain called GABA receptors, found in many animal species.

With the publication of the work this week in Science¹, oxazepam joins a growing list of pharmaceuticals that escape wastewater treatment unscathed, and may be medicating freshwater communities. Previous laboratory studies have shown that the contraceptive 17-ß-estradiol and the antidepressant drug fluoxetine – better known as Prozac -- altered behaviour in the fathead minnow (Pimephales promelas). The popular anti-inflammatory drug ibuprofen, meanwhile, reduced courtship behaviour in male zebrafish (Danio rerio).

All together, the evidence suggests that tests of possible pollutants mut go beyond merely cataloguing fatal or highly toxic doses, says Todd Royer, an ecologist at Indiana University in Bloomington. “This study really highlights the importance of nonlethal effects,” says Royer, who was not involved in the work. “Those nonlethal effects may alter community structure and other ecosystem processes despite the lack of direct mortality or acute toxicity.”

Swedish fish

To track down the nonlethal effects of oxazepam, Tomas Brodin of Umeå University in Sweden and his colleagues began by measuring the drug’s concentration in the Fyris River, a small watershed in a densely populated region of Sweden. They found that the European perch (Perca fluviatilis) accumulated the drug in its muscle tissue, at concentrations over six times that found in the river water.

Exposing perch to slightly higher concentrations of oxazepam in laboratory aquariums dramatically altered their behaviour, says Micael Jonsson, an ecologist at Umeå University and a coauthor on the study. Nonmedicated perch are timid, preferring to stick to familiar territory, and occasionally peeking out into the wider tank. Medicated fish, in contrast, embraced the unknown, readily swimming into uncharted territory.

Nonmedicated perch also prefer safety in numbers, and swim toward other fish of the same species. Medicated perch, however, turned away from their compatriots. Fish exposed to oxazepam were also quicker to feast on zooplankton introduced into the tanks.

At first, Jonsson, says, the researchers were surprised: “Antianxiety drugs are viewed as calming and soothing, but in fish it was the opposite,” he says. But the researchers decided the fish might be less inhibited by fear when exposed to the medication. “If the fish were anxious to begin with, perhaps the drug reduces anxiety and allows the fish to become more active,” says Jonsson.

A medicated ecosystem

More aggressive feeding in medicated fish, if it occurs in the wild, could affect the surrounding ecosystem, says Jonsson. Young perch feed on zooplankton, which, in turn, eat algae. If drugged fish gobble more zooplankton, algae may thrive – and perhaps also bloom.

But it is difficult to extrapolate from the laboratory to a natural setting. For example, Jonsson notes the ecological effects of oxazepam’s effects on appetite may be offset by increased predation, if emboldened perch find themselves easier prey.

“How this laboratory work would translate to effects in wild populations is a big guess,” agrees Charles Tyler, an ecotoxicologist at Exeter University in the United Kingdom who was not involved with the study. “We have no idea of the resilience of those populations in the wild.”