Bradycardic responses to microinjection of N-methyl-D-aspartate into the nucleus tractus solitarius are inhibited by local activation of 5-HT(3) receptors

Neuropharmacology. 2000 Sep;39(12):2336-45. doi: 10.1016/s0028-3908(00)00093-9.

Abstract

Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of heart rate, and that such a control can be inhibited by NTS-5-HT(3) receptor stimulation. In the present study, we examined in urethane anaesthetized rats the effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPBG), a potent and selective 5-HT(3) receptor agonist, on the cardiovascular responses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascular responses to intra-NTS microinjections of AMPA or kainic acid. The reduction by CPBG of the NMDA-evoked cardiac response was blocked by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, as well as bicuculline, a GABA(A) receptor antagonist. These results suggest that the stimulation of NTS 5-HT(3) receptors specifically reduces, via a GABA-dependent mechanism, the cardiac response to local NMDA administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baroreflex / drug effects
  • Bicuculline / pharmacology
  • Biguanides / pharmacology
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / pharmacology*
  • GABA Antagonists / pharmacology
  • Granisetron / pharmacology
  • Heart Rate / drug effects*
  • Hemodynamics / drug effects
  • Male
  • Microinjections
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Solitary Nucleus / physiology*
  • Sympathetic Nervous System / drug effects
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Biguanides
  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Receptors, Kainic Acid
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • 1-(3-chlorophenyl)biguanide
  • Granisetron
  • Bicuculline