The role of central 5-HT3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats

J Physiol. 2005 Aug 1;566(Pt 3):939-53. doi: 10.1113/jphysiol.2005.085845. Epub 2005 May 19.


Brainstem 5-hydroxytryptamine (5-HT, serotonin)-containing neurones modulate cardiovascular reflex responses but the differing roles of the many 5-HT receptors have not been thoroughly investigated. The present experiments on anaesthetized rats investigated the role of 5-HT3 receptors in modulating vagal afferent evoked activity of nucleus tractus solitarius (NTS) neurones. Recordings were made from 301 NTS neurones receiving an input at long (> 20 ms) minimum onset latency from stimulation of the vagus nerve. These included 140 neurones excited by activating non-myelinated cardiopulmonary afferents by right atrial injection of phenylbiguanide (PBG). Ionophoretic application of PBG, a highly selective 5-HT3 receptor agonist, significantly increased activity (from 2.4 +/- 0.4 to 5.5 +/- 0.8 spikes s(-1)) in 96 of 106 neurones tested and in all 17 neurones tested the increase in activity (3.4 +/- 1.1 to 7.0 +/- 1.9 spikes s(-1)) was significantly attenuated (3.0 +/- 0.9 to 3.8 +/- 1.1 spikes s(-1)) by the selective 5-HT3 receptor antagonist granisetron. Ionophoretic application of PBG potentiated responses to vagus nerve and cardiopulmonary afferent stimulation, and granisetron significantly attenuated this cardiopulmonary input (20.2 +/- 5.7 to 10.6 +/- 4.1 spikes burst(-1)) in 9 of 10 neurones tested. Ionophoretic application of AMPA and NMDA also excited NTS neurones and these excitations could be selectively antagonized by the non-NMDA and NMDA receptor antagonists DNQX and AP-5, respectively. At these selective currents, DNQX and AP-5 also attenuated PBG- and cardiopulmonary input-evoked increases in NTS activity. These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT3 receptors. This excitatory response to 5-HT3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Anesthesia
  • Animals
  • Feedback / physiology
  • Male
  • Neurons / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Reflex / physiology*
  • Solitary Nucleus / physiology*
  • Vagus Nerve / physiology*


  • Receptors, Serotonin, 5-HT3