Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation.
1. 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. 2. 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 with the 5-hydroxytryptamine (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.
Roberts
M H
MH
Department of Physiology, University College Cardiff.
Davies
M
M
Girdlestone
D
D
Foster
G A
GA
D000818:Animals; D004558:Electric Stimulation; D007478:Iontophoresis; D008297:Male; D008839:Microelectrodes; D009046:Motor Neurons / Q000187:drug effects*; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology
D012702:Serotonin Antagonists; D012701:Serotonin