Activation of 5-HT2 receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate

Eur J Pharmacol. 1993 Feb 16;231(3):347-54. doi: 10.1016/0014-2999(93)90109-u.

Abstract

The interaction between serotonin and excitatory amino acid agonists at rat neocortical neurons was investigated using the grease-gap recording method. Depolarization evoked by 50 microM N-methyl-D-aspartate was dose dependently facilitated by serotonin (5-HT) (1 to 100 microM) giving a bell-shaped dose-response curve with maximum enhancement at 30 microM. In contrast, quisqualate and kainate depolarizations were not enhanced. Subnanomolar concentrations of methysergide, ritanserin and spiperone, but not ICS 205-930, attenuated the 5-HT enhancement, compatible with 5-HT2, but not 5-HT1 or 5-HT3 receptor subtype involvement. Enhancement was observed with 5-HT2 receptor agonists, whereas 5-HT1 receptor subtype agonists had either no effect (1B and 1C) or reduced (1A) the N-methyl-D-aspartate depolarization. Scopolamine and prazosin reduced the N-methyl-D-aspartate depolarization and blocked facilitation induced by carbachol and phenylephrine, but not that due to 5-HT. Tetrodotoxin reduced the N-methyl-D-aspartate depolarization, but the facilitation by 5-HT persisted. Activators of protein kinase C (phorbol diacetate and 1-oleoyl-2-acetyl-sn-glycerol) did not mimic the serotonin facilitation. We conclude that serotonin enhances N-methyl-D-aspartate depolarization of rat cortical neurons through activation of 5-HT2 receptors, however the cellular mechanism underlying the facilitation remains to be established.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • N-Methylaspartate / pharmacology*
  • Neurons / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • N-Methylaspartate