EFFECTS OF 5-HT AND 5-HT1A RECEPTOR AGONISTS AND ANTAGONISTS ON DORSAL VAGAL PREGANGLIONIC NEURONS IN ANESTHETIZED RATS - AN IONOPHORETIC STUDY

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 p entobarbitone sodium or chloral hydrate-anaesthetized rats, respective ly. 2 Extracellular recordings were made from 176 preganglionic neuron es in the dorsal vagal nucleus (DVN). Application of 5-HT at low curre nts (less than or equal to 10 nA) increased the activity of these neur ones. However, at increased currents (10-60 nA), it had a predominantl y depressant effect. Application of selective 5-HT1A receptor antagoni sts, (+/-)-pindolol or WAY-100635, attenuated the excitatory responses evoked by 5-HT. 3 Ionophoresis of the 5-HT1A receptor agonist, 8-hydr oxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-30 nA) increased the f iring rate of 19 and decreased that of 67 of the 104 vagal neurones te sted. Other 5-HT1A receptor agonists, flesinoxan and N,N-di-n-propyl-5 -carboxamidotryptamine (DP-5-CT) also had predominantly depressant eff ects. 4 (+/-)-Pindolol attenuated excitations but not inhibitions evok ed by 8-OH-DPAT. Surprisingly, WAY-100635 and 8-OH-DPAT produced the s ame effect on these neurones and when applied together, WAY-100635 fai led to attenuate the 8-OH-DPAT responses. 5 Dorsal raphe neurones were identified by their low, regular firing rate and their subsequent his tological localization. 8-OH-DPAT reversibly reduced the activity in a ll 7 neurones tested and this was antagonized by WAY-100635 in all 3 n eurones tested. 6 In conclusion, 5-HT applied to vagal preganglionic n eurones evokes excitatory and inhibitory responses. The excitatory, bu t not the inhibitory responses may be mediated, at least in part, by a ctivation of 5-HT1A receptors.