Neonatal fluoxetine exposure affects the neuronal structure in the somatosensory cortex and somatosensory-related behaviors in adolescent rats

Neurotox Res. 2009 Apr;15(3):212-23. doi: 10.1007/s12640-009-9022-4. Epub 2009 Mar 4.


Selective serotonin reuptake inhibitor (SSRI)-type antidepressants are often prescribed to depressive pregnant women for their less adverse side effects. However, growing evidences have shown increased congenital malformations and poor neonatal adaptation in the perinatal SSRI-exposed human infants as well as animal pups. In this study, we examined the effects of early exposure of fluoxetine, the most popular SSRI-type antidepressant, on the developing somatosensory system. Physiological saline or fluoxetine (10 mg/kg) was subcutaneously injected into neonatal rats from P0 to P6. Somatosensory-related behaviors were examined in adolescence (P30-P35). Morphological features of the primary somatosensory cortex were checked at P7 and P35. The tactile and thermal perceptions as well as locomotor activity were affected by neonatal fluoxetine treatment. At the morphological level, the number of branch tips of thalamocortical afferents to the somatosensory cortex was reduced in the fluoxetine-treated rats. Furthermore, the spiny stellate neurons in the layer IV somatosensory cortex had reduced dendritic span and complexity with fewer branches, shorter dendritic length, and smaller dendritic field. The spine density of spiny stellate neurons was significantly reduced whereas the spine length of mushroom- and branched-type was increased. Taken together, these results indicate that neonatal fluoxetine administration has long-lasting effects on the function and structure in the somatosensory system. Sensory information processing may be disturbed in the neonatal fluoxetine-treated animals due to the structural deformation in the thalamocortical afferents and dendritic structures of the spiny stellate neurons in the layer IV somatosensory cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / physiology
  • Age Factors
  • Amino Acids
  • Animals
  • Animals, Newborn
  • Axons / drug effects
  • Axons / ultrastructure
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Dendrites / drug effects
  • Dendrites / ultrastructure
  • Exploratory Behavior / drug effects
  • Female
  • Fluoxetine / pharmacology*
  • Locomotion / drug effects
  • Male
  • Neurons / cytology
  • Neurons / drug effects*
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Sensory Deprivation / physiology
  • Serotonin Uptake Inhibitors / pharmacology*
  • Silver Staining / methods
  • Somatosensory Cortex / cytology*
  • Somatosensory Cortex / drug effects*
  • Thalamus / cytology
  • Thalamus / physiology


  • Amino Acids
  • Serotonin Uptake Inhibitors
  • dolaisoleucine
  • Fluoxetine