Neonatal fluoxetine exposure affects the action potential properties and dendritic development in cortical subplate neurons of rats

Abstract

Selective serotonin reuptake inhibitor (SSRI)-type antidepressants might be given to depressive pregnant women and the developing fetuses are thus exposed to these drugs. Since serotonin plays important roles in the maturation of the nervous system, early SSRI exposure might influence the fetal brain development. To test this hypothesis, we treated the neonatal rat pups with fluoxetine (Flx) from the day of birth to postnatal day (P) 4, comparable to the third trimester of human gestation, and observed the physiological and morphological features of subplate neurons (SPns), a group of cells important for early cortical development and vulnerable to neonatal neural insults. Using whole-cell patch-clamp recording technique, we examined the passive membrane properties and characteristics of action potential (AP). In SPns of Flx-treated rats, the rheobase for generating an AP was increased and the width of APs was reduced, especially in the falling phase. In the morphological aspect, the dendritic remodeling of SPns including dendritic branching, elongation and pruning were affected by early Flx treatment. Together, our results demonstrate that the teratogenic effect of early SSRI exposure on the structure and function of developing SPns and these changes may lead to undesired brain activity and distorted behaviors later in life.