Fish exposed to the antidepressant drug Prozac continues the behavior of the next three generations and raises questions about what may happen to humans whose mothers take the drug.
At the University of Ottawa, researchers exposed Vance Trudeau and Marilyn Vera-Chang fish eggs and freshly cut fish to Prozac levels that were typical of what would cross the human placenta and reach an embryo.
Trudeau and others had already studied the side effects of these substances in fish for years and focused on potential effects on reproduction.
He and Vera-Chang say they felt that the next step should be to look at changes in the reproductive systems of the next generation of fish – progeny of fish exposed to Prozac. Both researchers study the effects of hormones on the brain.
But the effects they found were a whole new kind: they were changes in the behavior of the fish.
"They acted very strangely and their stress response was strange," said Trudeau in an interview.
Many fish species have a way to explore unknown surroundings, such as a new tank. They swim up, down and around, adapting to the new home. In nature, this behavior helps them figure out when to hunt for food and when to hide.
But fish that were exposed to Prozac when they were still in the egg did not study much. They swam to the bottom of the tank and remained for the most part there.
"These kind of exploratory behaviors are super important in all vertebrates. It's a kind of coping behavior," where an animal learns to handle the surroundings, "said Trudeau.
While the experiment only investigated Prozac, Trudeau said that he expects similar results to come from other members of his class of antidepressants, all of which are targeted at a brain drug called serotonin.
"What we found is that (the change) continues for two generations," he said. He suspects an "epigenetic" effect in which children and grandchildren of the fish exposed to Prozac have normal genes, but something makes these genes turn their activity on and off in an unusual pattern.
"We call it transgeneral effects."
Levels of a stress hormone called cortisol were also unusual; they were lower than they should be.
While the experiments have so far used a common laboratory species called zebrafish, he says that there is a larger question about effects on humans.
"We are in generation 1.5 of fluoxetine (Prozac) use now. It came on the market in 1987."
Trudeau said he would "absolutely not" advise people who take this or other antidepressant medicine to stop.
"There are also great benefits for these types of drugs: In fact, they can be life-saving in some situations. However, it is important to follow a doctor's advice and take the prescribed dose. The future discussion should take into consideration that such medicine has long-term effects than we have ever imagined since our work clearly shows that what we do today can affect future generations, "he said.
There are indications that children of women taking the drug during pregnancy have low cortisol and are "slightly more brave" than other children.
"It was known and our major question was: Is it gone? What about their children? … What are the consequences for people?"
He said other antidepressants probably also have lasting effects, but his experiment used only Prozac.
MORE: How can the substances we take affect our children or grandchildren?
For Vera-Chang, work was the basis for her PhD study. She has spent three years working with approx. 6,000 zebrafish, even in the lab at Christmas to feed them and keep their mind in order.
"It was a really challenging study," she said. "The variables should be consistent generation by generation" to ensure that the results were caused by the substance and not by changes in food, temperature or water or even the person who fed.
"A short dose can actually affect future generations – six days early in life," she said.
Their paper is published this week in PNAS, one of the world's three leading scientific journals.
Outside the laboratory, Prozac affects wildlife because it enters lakes and rivers, Trudeau said. The active chemicals remain stable, even if the body expels them into the urine, and the treatment plants do not remove drugs.
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