New paper: Antidepressant use during pregnancy leads to less detailed investigation strategies in novel environments in the offspring.

Fluoxetine is a so-called selective serotonin reuptake inhibitor (SSRI), which increases the concentration of the signal molecule serotonin in the small gaps between brain cells. The mechanism behind the antidepressant effect of SSRIs is still unclear, but elevated levels of serotonin may play a role. A problem, however, is that serotonin also has a role in the development of the brain of a fetus. The elevated serotonin levels during development caused by the SSRI treatment of the mother could thus, in theory, have an unwanted effect on the children.

Previous research with humans showed that children that were exposed to SSRIs can sometimes have a different social-emotional development. Some even suggested that the risk for autism spectrum disorders (ASD) is higher. But pregnant women only use antidepressants because they are depressed, which in itself is known for having effects on the child.

In order to make sure that we only study the effects of the drug, and not the effect of depression, we use animals in our research. Healthy female rats were treated with fluoxetine (or a control substance) during the period of pregnancy and breastfeeding. Their pups were allowed to grow up and then tested (at adult age) in a seminatural environment. This seminatural environment simulates the natural environment, and allows us to study in detail how each animal behaves and interacts with its environment and the other animals. Previously, we found that female rats that were previously exposed to SSRIs via their mothers showed reduced levels of social and prosocial behavior, while male rats struggle with coping with stressful situations. 

In the current study, we were interested in how the fluoxetine exposed animals behave in a situation in a relative stressful situation in which they are exposed to a novel environment with unfamiliar other rats. Therefore, we studied their behavior during the first hour after introduction to this seminatural environment and were interested in what strategy they would use to explore the unfamiliar environment (non-social investigation) and in meeting other rats (social investigation). The results showed that rats that were perinatally exposed to fuoxetine used different aspects of non-social investigation behaviors, while normal social investigation behaviors were used. More specifically, both fluoxetine-exposed males and female rats spent more total time running around the environment than control rats whose mothers did receive the placebo. Furthermore, fluoxetine-exposed females spent less time exploring objects and specific elements in the environment. Altogether, this suggest that SSRIs during pregnancy could lead to changes in behavior in the children later in life. It can lead to a quicker, less detailed investigation strategy in novel environments, especially in female offspring.

This study is part of a collaboration between our group at UiT The Arctic University of Norway and the University of Groningen. It was funded by Helse Nord RHF.

[Summary by Eelke]

Sylte, O.C., Johansen, J.S., Heinla, I., Houwing, D.J., Olivier, J.D.A., Heijkoop, R., Snoeren, E.M.S. (2021). Effects of perinatal fluoxetine exposure on novelty-induced social and non-social investigation behaviors in a seminatural environment. Psychopharmacology.