Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat

Eur Neuropsychopharmacol. 2007 May-Jun;17(6-7):417-29. doi: 10.1016/j.euroneuro.2006.08.009. Epub 2006 Dec 19.


Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-regulated gene 2, but increased mRNA for neuron-specific enolase (NSE) in both stressed and unstressed animals having no effect on stress-induced upregulation of NSE protein. These findings demonstrate that in the dorsal raphe nucleus of chronically stressed rats, citalopram normalizes TPH expression and blocks stress effects on distinct genes related to neurotransmitter release and neuroplasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citalopram / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Male
  • Models, Animal
  • Polymerase Chain Reaction
  • RNA / genetics
  • RNA / isolation & purification
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Wistar
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / adverse effects*
  • Social Behavior
  • Stress, Physiological / chemically induced
  • Stress, Physiological / genetics*
  • Stress, Physiological / physiopathology*
  • Tryptophan Hydroxylase / genetics*


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin
  • RNA
  • Tryptophan Hydroxylase