PT  - JOURNAL ARTICLE
AU  - Hosford, Patrick S
AU  - Mifflin, Steve W.
AU  - Ramage, Andrew G
TI  - 5-hydroxytryptamine mediated neurotransmission modulates spontaneous and vagal evoked glutamate release in the nucleus tractus solitary (NTS) - effect of uptake blockade
AID  - 10.1124/jpet.113.211334
DP  - 2014 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.113.211334
4099  - http://jpet.aspetjournals.org/content/early/2014/03/11/jpet.113.211334.short
4100  - http://jpet.aspetjournals.org/content/early/2014/03/11/jpet.113.211334.full
AB  - The effect of blockade of either 5-HT/serotonin transporter (5-HTT/SERT) with citalopram or the organic cation transporter 3 (OCT3)/plasma membrane monoamine transporter (PMAT) with decynium-22 on spontaneous and evoked release of 5-HT in the NTS was investigated in the rat brainstem slice treated with gabazine. 5-HT release was measured indirectly by changes in frequency and amplitude of glutamatergic mEPSCs (in the presence of TTX) and evoked EPSCs. Blockade of 5 HT3 receptors with granisetron reduced, while the 5-HT3 agonist phenylbiguanide, increased the frequency of mEPSCs. 5 HT decreased mEPSC frequency at low, and increased frequency at high concentrations. This inhibition was blocked by the 5-HT1A antagonist WAY-100635, which was ineffective on its own, while the excitation was reversed by granisetron. Addition of citalopram or decynium-22 caused inhibition, which was prevented by 5-HT1A blockade. Thus in the NTS the spontaneous release of 5-HT is able activate 5-HT3 receptors but not 5 HT1A receptors as the release in their vicinity is removed by uptake. The ineffectiveness of corticosterone suggests that the low affinity, high capacity transporter is PMAT not OCT3. For evoked 5-HT release only decynium-22 caused an increase in amplitude of EPSCs, with a decrease in the paired pulse ratio and increased the number of spontaneous EPSCs after 20Hz stimulation. Thus for the evoked release of 5 HT the low affinity, high capacity transporter PMAT but not the 5 HTT/SERT is important in the regulation of changes in 5-HT extracellular concentration.