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The role of central 5‐HT 3 receptors in vagal reflex inputs to neurones in the nucleus tractus solitarius of anaesthetized rats
Author(s) -
Jeggo Ross D.,
Kellett Daniel O.,
Wang Yun,
Ramage Andrew G.,
Jordan David
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.085845
Subject(s) - dnqx , solitary nucleus , vagus nerve , chemistry , stimulation , reflex , granisetron , agonist , endocrinology , medicine , serotonin , receptor , glutamate receptor , neuroscience , ampa receptor , biology , antiemetic , vomiting
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‐HT 3 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‐HT 3 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‐HT 3 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‐HT 3 receptors. This excitatory response to 5‐HT 3 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.