In a new study, researchers found anhedonia, cognitive deficits, and impulsivity in rats born to mothers given fluoxetine (Prozac) during pregnancy or while breastfeeding.
The findings were sex-dependent, with male rats exhibiting anhedonia and female rats exhibiting cognitive deficits and impulsivity (anhedonia is a term for the inability to feel pleasure or joy). The impact on male rats was worse if their mothers received Prozac during pregnancy, while the impact on female rats was worse if their mothers received Prozac during breastfeeding.
“The results presented in this study suggest that perinatal pharmacological manipulation of the serotonergic system leads to age- and sex-dependent effects indicating that males should be studied primarily for anhedonic-like symptoms whereas cognitive dysfunction should be first investigated in female rats,” the researchers write.
Moreover, mothers who received Prozac had fewer babies and babies with lower birth weights. Mothers who received Prozac while breastfeeding, specifically, found their children continued to have lower body weight into adulthood.
“These data suggest that the prenatal alteration of the serotonergic system results in a reduced birth rate and lower-weight offspring. However, pups exposed to prenatal FLX regained weight at weaning. Conversely, early postnatal exposure to FLX is associated with lower body weight that persists during the lifetime,” the researchers write.
The researchers also found that rats born of mothers given Prozac ended up with many differences in terms of brain development and gene expression compared with rats whose mothers did not receive the drug.
They noted that their findings “[support] previous evidence showing that serotonin alterations have a huge impact on the inflammatory system, which is indeed long-lasting.”
The study was conducted by researchers at the Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti,” Universita Degli Studi di Milano, Milan, Italy. It was published in the journal Brain, Behavior, and Immunity.
The researchers used the sucrose preference test to assess anhedonia, the novel objects recognition test to evaluate cognitive functioning, and the elevated plus maze test to assess impulsivity. Whether these tests serve as an exact enough map of human experiences is an open question, but they are standard for assessing such responses in animal studies.
The researchers do not address the implications of their study for human mothers using antidepressants or the potential impacts on their children. Instead, the researchers frame their study as somehow exploring the natural role of serotonin—even though their study was explicitly about using an antidepressant to disrupt the serotonin system:
“The current study supports the idea that the pharmacological manipulation of the serotonergic system could be used as a tool to explore the role of serotonin during brain development and its involvement in the development of psychiatric disorders,” they write.
Despite this oversight, there is plenty of research on the adverse impacts of antidepressant drugs used in pregnancy.
Researchers have argued that antidepressants should be discontinued in pregnancy because of the risk of neonatal withdrawal syndrome. Studies have consistently found antidepressant use in pregnancy to be associated with numerous risks to neonatal health, including neonatal withdrawal syndrome, preterm birth, birth defects, developmental problems, cardiopulmonary problems, and even death.
Some studies have even accounted for preexisting factors like depression severity by comparing women who continued using antidepressants during pregnancy with women who had the same indication and did use antidepressants initially—but stopped after becoming pregnant. Those who continued to use antidepressants had an increased risk of neonatal health complications, including preterm birth, low birth weight, and hospitalizations in their newborns, compared with mothers who stopped using the drugs during pregnancy.
Gallo, M. T., Brivio, P., Dolci, B., Fumagalli, F., & Calabrese, F. (2023). Perinatal serotonergic manipulation shapes anhedonic and cognitive behaviors in a sex- and age-dependent manner: Identification of related biological functions at central and peripheral level. Brain, Behavior, and Immunity, 114, 118-130. https://doi.org/10.1016/j.bbi.2023.08.016 (Link)