Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptors: an electrophysiological study in the rat brain

Naunyn Schmiedebergs Arch Pharmacol. 1988 Mar;337(3):246-54. doi: 10.1007/BF00168834.


5-HT-containing terminals possess autoreceptors which modulate the release of 5-HT into the synaptic cleft. Tritiated imipramine ([3H]IMI), and more specifically [3H]citalopram and [3H]paroxetine, bind to a site associated with the 5-HT reuptake carrier on the 5-HT terminals. The function of terminal 5-HT autoreceptors is decreased following long-term treatment with the 5-HT reuptake blocker citalopram. The present study was undertaken to determine whether an increased synaptic availability of 5-HT or, the occupation of the [3H]IMI site, were responsible for this modification. Unitary extracellular recordings were obtained from CA3 dorsal hippocampus pyramidal neurons under chloral hydrate anesthesia in rats treated daily with fluoxetine (10 mg/kg/day X 14 days), a selective 5-HT reuptake blocker, or clorgyline (1 mg/kg/day X 21 days), an inhibitor of type A monoamine oxidase. The function of the terminal 5-HT autoreceptors was assessed by comparing the effectiveness of the electrical stimulation of the ascending 5-HT pathway on the firing activity of hippocampus pyramidal neurons prior to, and following, the administration of methiothepin, an antagonist of the terminal 5-HT autoreceptor, and, by determining the ratio of effectiveness of 0.8 Hz (S1) and 5 Hz (S2) stimulations. Long-term administration of fluoxetine or clorgyline both increased the efficacy of the stimulation of the 5-HT pathway. However, the enhancing effect of methiothepin on the efficacy of the stimulation was attenuated by the fluoxetine, but not by the clorgyline, treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Clorgyline / pharmacology
  • Electric Stimulation
  • Electrophysiology
  • Fluoxetine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • In Vitro Techniques
  • Iontophoresis
  • Male
  • Methiothepin / pharmacology
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / pharmacology*


  • Monoamine Oxidase Inhibitors
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Fluoxetine
  • Methiothepin
  • Clorgyline