Pre-weaning fluoxetine exposure perturbs social behavior at adulthood via altering hippocampal morphometry and PSD-95...

The depression during and after pregnancy cause significant exposure of fluoxetine to the child at early life through mother. This exposure to the child, during the vulnerable window of development, can have a long lasting impact on overall mental wellbeing. Long term neurobehavioral aspect of developmental toxicity is neglected as the part of testing requirements in the process of drug developmental. In this context, the present study was designed to study the possible effect of pre-weaning fluoxetine exposure on the social behavior of rats upon adulthood followed by assessing hippocampal morphometry (hematoxylin-eosin and silver staining) and post-synaptic density protein 95 (PSD-95) expression (using qPCR). Our data showed that the fluoxetine exposure (10, 50 and 100mg/kg) caused predominant increase in the social behavior of rats; the effect more pronounced in female rats. The morphometric analysis revealed significant increase in cell population and count of dentate gyrus (DG) region of hippocampus along with enhanced dendritic arborization. Furthermore, the PSD-95 expression was found to be down regulated in the fluoxetine treated group as compared to control. In conclusion, the present study demonstrate that the early post-natal exposure to fluoxetine cause hypersociability upon attaining adulthood, which may be attributed to enhanced neuronal proliferation and decrease PSD-95 expression in the hippocampus.