Behaviours differ in male and female fish three generations after Prozac exposure
Prozac can lower cortisol in zebrafish, affecting their exploration and responses to stress, according to a recent U of O study.
“A common pharmaceutical agent that millions of people take can have an effect for up to three generations,” U of O Research Chair in Neuroendocrinology and biology professor, Vance Trudeau, told the Fulcrum.
For four days, Trudeau’s team exposed zebrafish to Prozac as embryos. Shortly after hatching, the fish were showing lower cortisol levels compared to those not exposed to the drug. When exposed to stress or new environments, the male fish responded less.
The study, published in December 2018 in the Proceedings of the National Academy of Sciences of the United States of America, concluded Prozac-induced “decreases in cortisol and behaviors … led (them) to the hypothesis that cortisol regulates locomotor and exploratory behaviours.”
Trudeau said exploratory behaviour is linked to fundamental tasks, such as finding hiding places, and food. Fish two generations after the Prozac exposure also showed abnormal behaviour.
Photo: Parker Townes.
“The ones that were treated, even two generations before, they kind of swim at the bottom,” he said.
Motivated by research suggesting child weight may be affected by mothers taking antidepressants, the researchers used zebrafish because they share a similar stress system with humans.
The researchers found that when cortisol was reintroduced, exploratory behaviour in males returned.
“We gave them cortisol for three days only, and then they started swimming on the top again,” said Trudeau. “Actually, they overshot; they started swimming like mad.”
Differences between male and female fish were also noted in the study.
“Any individual, let’s say human, that may have a compromised stress response—just like a fish —won’t be able to cope very well with challenges.”
—Vance Trudeau, U of O Research Chair in Neuroendocrinology and biology professor.
When stressed, like being taken from their tanks, male zebrafish responded less compared to those unexposed to Prozac. Female zebrafish, however, responded more.
The study suggests the differences may be because of “sex-specific levels of sex steroids in addition to sex-based variability in (drug absorption)”.
“The males—the cortisol bottoms out, and the exploratory behaviour goes down,” said Trudeau. “The females—the exploratory behaviours go up, but it’s also caused by the cortisol change.”
Trudeau added that cortisol can have many effects, so additional problems may also be present after Prozac exposure.
“Any individual, let’s say human, that may have a compromised stress response—just like a fish —won’t be able to cope very well with challenges,” he said.
Addressing criticism that the study looks at healthy fish rather than humans with depression, Trudeau says the study is still relevant for understanding fish behaviour, and the environment. He says if fish are exposed to Prozac through sewage water during breeding season, it could affect fish the following year.
“That doesn’t say that it will have an effect for three generations in psychiatric patients, but it does say that it has an effect.”
Building on this study, current research at the U of O will analyze where cortisol is acting in the brain, sex differences, and sensitive phases in the early development of zebrafish.
For anyone currently taking Prozac, Trudeau says doctors should be consulted before changes are made to prescriptions.