Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

BMC Neurosci. 2012 Jan 5;13:5. doi: 10.1186/1471-2202-13-5.


Background: Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents.

Results: We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of middle-aged (8 months old) rats. The density of puncta expressing PSA-NCAM increased in the dorsal cingulate cortex, as well as in different hippocampal and amygdaloid regions. In these later regions there were also increases in the density of puncta expressing glutamic acid decarboxylase 65/67 (GAD6), synaptophysin (SYN), PSA-NCAM/SYN and PSA-NCAM/GAD6, but a decrease of those expressing vesicular glutamate transporter 1 (VGluT1). Since there is controversy on the effects of antidepressants on neurogenesis during aging, we analyzed the number of proliferating cells expressing Ki67 and that of immature neurons expressing doublecortin or PSA-NCAM. No significant changes were found in the subgranular zone, but the number of proliferating cells decreased in the subventricular zone.

Conclusions: These results indicate that the effects of fluoxetine in middle-aged rats are different to those previously described in young-adult animals, being more restricted in the mPFC and even following an opposite direction in the amygdala or the subventricular zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Body Weight / drug effects
  • Cell Count
  • Cell Proliferation / drug effects
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Fluoxetine / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Glutamate Decarboxylase / metabolism
  • Ki-67 Antigen / metabolism
  • Lateral Ventricles / cytology
  • Lateral Ventricles / drug effects
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism*
  • Neurogenesis / drug effects*
  • Neuropeptides / metabolism
  • Rats
  • Rats, Wistar
  • Sialic Acids / genetics
  • Sialic Acids / metabolism*
  • Synaptophysin / metabolism
  • Telencephalon / cytology
  • Telencephalon / drug effects*
  • Vesicular Glutamate Transport Protein 1 / metabolism


  • Antidepressive Agents, Second-Generation
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neural Cell Adhesion Molecule L1
  • Neuropeptides
  • Sialic Acids
  • Synaptophysin
  • Vesicular Glutamate Transport Protein 1
  • polysialyl neural cell adhesion molecule
  • Fluoxetine
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2