Feedback stimulation of somatodendritic serotonin release: a 5-HT3 receptor-mediated effect in the raphe nuclei of the rat

Brain Res Bull. 1998;45(2):203-8. doi: 10.1016/s0361-9230(97)00340-7.

Abstract

Slices from rat midbrain containing the raphe nuclei and from hippocampus were prepared, loaded with [3H]5-HT and superfused and the resting and the electrically stimulated [3H]5-HT release was measured. The 5-HT3 receptor agonist 2-methyl-5-HT (1 to 10 micromol/l) increased the resting tritium outflow in superfused raphe nuclei slices, EC50 5.3 micromol/l. The 2-methyl-5-HT-induced increase of tritium outflow was an external Ca2+-independent process and was not altered by reserpine pretreatment but it was reversed by addition of the 5-HT uptake inhibitor fluoxetine (1 micromol/l). The 5-HT3 receptor antagonists ondansetron and GYKI-46 903 (1 micromol/l) did not antagonize the stimulatory effect of 2-methyl-5-HT on resting tritium outflow. 2-Methyl-5-HT in lower concentration increased the electrically induced tritium overflow from raphe nuclei slices (EC50 0.56 micromol/l) and also from hippocampal slices preloaded with [3H]5-HT. These effects were reversed by 1 micromol/l of ondansetron and GYKI-46903. The 5-HT3 receptor antagonists (1 micromol/l) were without effects on depolarization-evoked [3H]5-HT release at 2 Hz stimulation, when 10 Hz stimulation was used, ondansetron and GYKI-46 903 reduced the tritium overflow from raphe nuclei slices. These data indicate that 5-HT3 receptors positively alter depolarization-induced somatodendritic 5-HT release in the raphe nuclei. They also show that 2-methyl-5-HT is able to evoke 5-HT release not only from vesicles but also from cytoplasmic stores via a transporter-dependent exchange process.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Dendrites / metabolism*
  • Dendrites / physiology
  • Electric Stimulation
  • Feedback / physiology*
  • Fluoxetine / pharmacology
  • In Vitro Techniques
  • Male
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Neural Pathways / physiology
  • Ondansetron / pharmacology
  • Raphe Nuclei / metabolism*
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / metabolism*
  • Reserpine / pharmacology
  • Serotonin / analogs & derivatives
  • Serotonin / metabolism*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology

Substances

  • Adrenergic Uptake Inhibitors
  • Bridged Bicyclo Compounds, Heterocyclic
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • GYKI 46903
  • Serotonin
  • Ondansetron
  • 2-methyl-5-HT
  • Reserpine