Long-term consequences of neonatal fluoxetine exposure in adult rats

Dev Neurobiol. 2014 Oct;74(10):1038-51. doi: 10.1002/dneu.22185. Epub 2014 May 9.

Abstract

Serotonin (5-HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)-type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late-gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX-exposed adult male rats exhibited reduced locomotor activity and depression-like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX-exposed rats. When the levels of 5-HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long-lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI-type antidepressants during pregnancy should be considered.

Keywords: amygdala; dendrites; emotion; medial prefrontal cortex; serotonin; social interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / growth & development*
  • Brain / pathology
  • Brain / physiopathology
  • Dendrites / drug effects
  • Dendrites / pathology
  • Dendrites / physiology
  • Depression / chemically induced
  • Depression / pathology
  • Depression / physiopathology
  • Fluoxetine / toxicity*
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Motor Activity / physiology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / growth & development
  • Pyramidal Cells / pathology
  • Pyramidal Cells / physiopathology
  • Random Allocation
  • Rats, Wistar
  • Selective Serotonin Reuptake Inhibitors / toxicity*
  • Sensory Gating / physiology
  • Serotonin / metabolism
  • Social Behavior
  • Tryptophan Hydroxylase / metabolism

Substances

  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan Hydroxylase