Hosford, PS; (2014) The cardiovascular regulatory role of 5-HT in the nucleus tractus solitarius. Doctoral thesis , UCL (University College London).

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Abstract

The nucleus tractus solitarus (NTS) integrates afferent information to maintain cardiovascular homeostasis. Pharmacological experiments have indicated that 5-HT is released in this process. In vitro and in vivo experiments were carried out to measure this release. 5-HT was detected in the NTS indirectly, by measuring glutamatergic inward currents in the slice and directly by voltammetry in the anaesthetised rat. In the slice, the presence of tonic release of 5-HT was confirmed which, in part, is responsible for basal release of glutamate via activation of 5-HT3 receptors. Blockade of the high-affinity, low-capacity 5-HT transporter (5-HTT; SERT), with citalopram and the low-affinity, high-capacity transporters (organic cation transporter 3; OCT3 and the plasma membrane monoamine transporter; PMAT), with decynium-22 caused a 5-HT1A mediated decrease in glutamate release. Evoked glutamate release was only augmented by decynium-22. In experiments with anaesthetisia, a voltammetric scan optimised for 5-HT was used. Stimulation of cardiopulmonary, chemoreceptor and baroreceptor afferents as well as electrical stimulation of vagal afferents increased the electrochemical signal, which was calcium and frequency dependent. Synthesis inhibitors for 5-HT, but not for noradrenaline, decreased the signal confirming it was 5-HT. Decynium-22 increased the evoked signal but neither citalopram nor desipramine, at doses shown to selectively decrease the removal of 5-HT or noradrenaline, had any effect. Blockade of glutamate receptors with kynurenate reduced the evoked 5-HT by ~50% and this remaining 5-HT was potentiated by decynium-22. Preliminary data from rats with heart failure induced by coronary artery ligation found that glutamate and 5-HT transmission to be augmented within the NTS. These data show that 5-HT release is increased by activation of afferent input and this release is regulated by OCT3/PMAT not 5-HTT. This suggests that 5-HT may act, in part, as a volume transmitter in the NTS. This regulation may be affected by disease such as heart failure.

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