Effects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: electrophysiological studies in the rat brain

Naunyn Schmiedebergs Arch Pharmacol. 1986 Aug;333(4):342-8. doi: 10.1007/BF00500007.


Citalopram (CIT), is a selective serotonin (5-HT) reuptake blocker and a clinically effective antidepressant. The present electrophysiological studies were undertaken to investigate in vivo the acute and long-term effects of CIT administration on 5-HT neurotransmission. In a first series of experiments, a single dose of CIT (0.05-0.5 mg/kg) was administered intravenously to naive rats while recording the activity of a 5-HT-containing neuron in the nucleus raphe dorsalis. A dose-response relationship of the inhibitory effect of CIT on the firing activity of 5-HT neurons was obtained with an ED50 of 0.23 +/- 0.03 mg/kg. In a second series of experiments, rats were treated with CIT (20 mg/kg/day, i.p.) for 2, 7 and 14 days. In rats treated for 2 days, there was a marked reduction in the firing activity of 5-HT neurons in the nucleus raphe dorsalis; there was a partial recovery after 7 days and a complete recovery after 14 days of treatment. The response of 5-HT neurons to intravenously administered LSD was decreased in rats treated for 14 days with CIT, indicating a desensitization of the somatodendritic 5-HT autoreceptor. In a third series of experiments, carried out in rats treated with CIT (20 mg/kg/day, i.p.) for 14 days, the suppression of firing activity of CA3 hippocampal pyramidal neurons produced by microiontophoretically-applied 5-HT and by the electrical activation of the ascending 5-HT pathway was measured. Long-term treatment with CIT did not modify the responsiveness of these neurons to microiontophoretically-applied 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Citalopram
  • Electric Stimulation
  • Hippocampus / drug effects
  • Male
  • Methiothepin / pharmacology
  • Microelectrodes
  • Neurons / drug effects
  • Propylamines / pharmacology*
  • Pyramidal Tracts / drug effects
  • Raphe Nuclei / drug effects
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects*
  • Synaptic Transmission / drug effects


  • Propylamines
  • Receptors, Serotonin
  • Citalopram
  • Methiothepin