Postnatal fluoxetine treatment affects the development of serotonergic neurons in rats

The goal of the present study was to investigate morphological changes in the serotonergic neurons/terminals in the dorsal (DR) and median (MnR) raphe nuclei and on the hippocampal dentate gyrus (DG) in neonatal rats treated from the 1st to the 21st postnatal day with fluoxetine (10 mg/kg sc, daily) or drug vehicle (0.9% saline 1 ml/kg). The results show that postnatal chronic treatment with fluoxetine promoted: (1) a smaller body weight increase during the pre-weaning period; (2) smaller number of 5-HT neurons in the DR; (3) smaller 5-HT neuronal cell bodies (area, perimeter and diameter) in the DR and the MnR and (4) diminished serotonergic terminals in the DG. These data suggest that the development of the serotonergic system was impaired and that early exposure to fluoxetine damaged the morphology of 5-HT neurons in young adult rats. While these findings are consistent with other work, more studies are needed to better clarify the effects of postnatal chronic treatment with fluoxetine on the serotonergic system and, consequently, on the functions modulated by serotonin.

Research highlightsUse of antidepressant fluoxetine (a selective serotonin re-uptake inhibitor, SSRI) early in life promoted growth retardation and changed the morphology of the brain serotonergic system, causing: ▶ A smaller body weight increase during the pre-weaning period. ▶ Smaller number of 5-HT neurons in the dorsal raphe nucleus. ▶ Smaller 5-HT cell bodies in the dorsal and median raphe nuclei. ▶ Diminished serotonergic terminals in the hippocampal dentate gyrus.