Effects of 5‐HT and 5‐HT1A receptor agonists and antagonists on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study

Abstract

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. Extracellular recordings were made from 176 preganglionic neurones in the dorsal vagal nucleus (DVN). Application of 5‐HT at low currents (<10nA) 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. 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. (±)‐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. 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. 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. 1995 British Pharmacological Society