Pre-weaning fluoxetine exposure caused anti-depressant like behavior at adulthood via perturbing tryptophan metabolism in rats

The perinatal depression exposes the child to antidepressants during vulnerable window of development, which can chronically impact the mental wellbeing of new born. Active pharmaceuticals are not tested for this long term neurobehavioral aspect of toxicity during drug development process. Keeping this in view, the current study was designed to study the effect of pre-weaning fluoxetine exposure on depression-like behavior of the offspring upon attaining adulthood using FST (Forced swim test). Additionally, the brain tryptophan, 5-HT (5-hydroxytryptamine) and its metabolite 5-HIAA (5-hydroxyindoleacetic acid) levels were quantified using Enzyme linked Immunosorbent Assay (ELISA), while expression of SERT (serotonin receptor), 5-HT_1A receptor, TPH (tryptophan hydroxylase) genes were monitored using qPCR. Our data showed that pre-weaning fluoxetine (10, 50 or 100 mg/kg) exposure decreased depression-like behavior. The 5-HT and 5-HIAA levels showed declining trend. However, the 5-HT synthetic precursor i.e. tryptophan levels were found to be significantly elevated in both brain and plasma as compared to control rats. The gene expression study did not reveal any significant alterations as compared to control. In conclusion, the present study demonstrate that pre-weaning fluoxetine exposure decreased depression-like behavior upon adulthood via perturbing tryptophan metabolism.