Effects of 5‐HT and 5‐HT1Areceptor agonists and antagonists on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study

Abstract

1. Effects of ionophoretic administration of 5-hydroxytryptamine (5-HT) and selective 5-HT1A receptor agonists and antagonists on identified dorsal vagal preganglionic and dorsal raphe neurones were studied in pentobarbitone sodium or chloral hydrate-anaesthetized rats, respectively. 2. Extracellular recordings were made from 176 preganglionic neurones in the dorsal vagal nucleus (DVN). Application of 5-HT at low currents (< or = 10 nA) increased the activity of these neurones. However, at increased currents (10-60 nA), it had a predominantly depressant effect. Application of selective 5-HT1A receptor antagonists, (+/-)-pindolol or WAY-100635, attenuated the excitatory responses evoked by 5-HT. 3. Ionophoresis of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-30 nA) increased the firing rate of 19 and decreased that of 67 of the 104 vagal neurones tested. Other 5-HT1A receptor agonists, flesinoxan and N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) also had predominantly depressant effects. 4. (+/-)-Pindolol attenuated excitations but not inhibitions evoked by 8-OH-DPAT. Surprisingly, WAY-100635 and 8-OH-DPAT produced the same effect on these neurones and when applied together, WAY-100635 failed to attenuate the 8-OH-DPAT responses. 5. Dorsal raphe neurones were identified by their low, regular firing rate and their subsequent histological localization. 8-OH-DPAT reversibly reduced the activity in all 7 neurones tested and this was antagonized by WAY-100635 in all 3 neurones tested. 6. In conclusion, 5-HT applied to vagal preganglionic neurones evokes excitatory and inhibitory responses. The excitatory, but not the inhibitory responses may be mediated, at least in part, by activation of 5-HT1A receptors.