Effects of 5‐hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation

Abstract

The excitability of lumbar spinal motoneurones was studied in halothane‐anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots. Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of dl‐homocysteic acid into raphe obscurus but the response was not present in animals pretreated wtih the 5‐hydroxytryptamine (5‐HT) neurotoxin 5,7‐dihydroxytryptamine (5,7‐DHT). Microiontophoretically applied 5‐HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5‐HT were larger in 5,7‐DHT‐pretreated animals. The effects of 5‐HT were potently mimicked by iontophoretically applied 5‐carboxamidotryptamine but 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) was without effect. Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5‐HT2 antagonist, did not antagonize the effects of 5‐HT. Neither did the 5‐HT3‐receptor antagonist MDL 72222 or the selective 5‐HT1 binding ligand cyanopindolol. The non‐selective 5‐HT1/5‐HT2‐receptor antagonist methysergide was an effective antagonist of both the effects of 5‐HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline. It is concluded that 5‐HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5‐HT1‐like receptor which appears to be different from the 5‐HT1A‐and the 5‐HT1B‐binding sites characterized by others. 1988 British Pharmacological Society