Co-exposure to fish oil or folic acid does not reverse effects in the progeny induced by maternal exposure to fluoxetine

• Rats exposed maternally to fluoxetine and folic acid or fish oil were evaluated.
• Fluoxetine exposure induced anxiety and decreased hippocampal BDNF levels.
• Folic acid exposure resulted in hyperactivity and increased BDNF levels.
• Fish oil exposure decreased eating behavior and BDNF levels.
• Neither folic acid or fish oil reversed fluoxetine-induced effects.

The serotonin reuptake inhibitor antidepressant fluoxetine (FLX) has been widely prescribed for the treatment of some diseases during pregnancy and/or lactation. Despite possible adverse effects observed in the progeny after maternal exposure to FLX, it is recognized that not treating a mother who has clinical indication for antidepressants may also impact negatively her well being and the fetal/newborn development. The present study investigated if two supplements already used by pregnant women, i.e., folic acid (FA) and fish oil (FO) could minimize effects in pubertal rats induced by maternal exposure to FLX during pregnancy and lactation. Evaluations included two behavioral tests (elevated plus maze and novelty-induced suppressed feeding) and quantification of brain derived neurotrophic factor (BDNF) in the hippocampus. Wistar rats were gavaged with FLX (5 mg/kg) or tap water associated or not with FA (3 mg/kg) or FO (1.3 mg/kg) during pregnancy and lactation. Pups exposed to FLX presented anxiety-like behavior and decreased hippocampal BDNF levels that were not influenced by co-exposure with FA or FO. FO exposure resulted in anxiety-like behavior, decreased BDNF levels and eating behavior whereas FA exposure increased BDNF and induced hyperactivity in the elevated plus maze. In conclusion, this study suggests that reduced hippocampal BDNF may play a role in the developmental neurotoxicity of FLX. FA and FO were not effective as employed in the present study but the search for alternatives to manage the risk of antidepressant exposure during pregnancy and/or lactation is likely to continue.