Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain

Synapse. 1987;1(5):470-80. doi: 10.1002/syn.890010511.


The sustained administration of the 5-HT1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5-HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons was markedly reduced, whereas those of 8-hydroxy-2-N,N-propylamino-tetralin (8-OH-DPAT) and of gepirone were unchanged; however, the responsiveness of 5-HT neurons to direct microiontophoretic application of 5-HT, LSD, 8-OH-DPAT, and gepirone, but not of GABA, was reduced. The responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. The effectiveness of the electrical stimulation of the ascending 5-HT pathway in reducing pyramidal neuron firing activity was not significantly modified in rats treated with gepirone for 14 days. Furthermore, this treatment did not alter the function of the terminal 5-HT autoreceptor. It is concluded that the progressive restoration of the firing activity of 5-HT neurons, due to a desensitization of the somatodendritic 5-HT autoreceptor, combined with the direct activation of normosensitive postsynaptic 5-HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5-HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Brain / physiology*
  • Electric Stimulation
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Lysergic Acid Diethylamide / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Pyrimidines / pharmacology*
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Reference Values
  • Serotonin / physiology*


  • Anti-Anxiety Agents
  • Pyrimidines
  • Receptors, Serotonin
  • Serotonin
  • Lysergic Acid Diethylamide
  • gepirone