Receptor subtypes mediating facilitation by serotonin of excitability of spinal motoneurons.
Serotonin receptor ligands, with differential affinity for subtypes of serotonin (5-HT) receptors, were administered intravenously or iontophoretically to urethane-anesthetized rats and the effects of these compounds on glutamate-evoked firing of spinal motoneurons were tested. The excitability of spinal motoneurons was markedly enhanced after intravenous administration of the selective 5-HT1A ligand 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT) in rats with acute spinal transections at C1. However, local application of DPAT, directly into the ventral horn by microiontophoresis, inhibited the glutamate-evoked firing of motoneurons in direct contrast to the facilitatory effects of iontophoretically applied 5-HT. The DPAT-induced inhibition may have been nonspecific, since it was not antagonized by methysergide. Other 5-HT agonists, with relatively selective affinity for 5-HT1B, 5-HT1C and 5-HT2 receptors, increased the excitability of spinal motoneurons when applied iontophoretically or intravenously. The excitatory effect of iontophoretically applied 5-HT was antagonized by the nonselective 5-HT antagonist, methysergide and by ketanserin and ritanserin, which have relatively selective affinity for 5-HT1C and 5-HT2 receptors. These results indicate that 5-HT1A receptors do not mediate facilitation of excitability of motoneurons produced by local application of 5-HT directly into the vicinity of the motoneurons. However, the marked increase in firing of motoneurons that was caused by intravenous administration of DPAT in spinal transected rats, suggests that 5-HT1A receptors in the spinal cord may participate in 5-HT-induced enhancement of somatomotor outflow, at sites presynaptic to the motoneurons. The iontophoretic results suggest that 5-HT1B, 5-HT1C and 5-HT2 receptors may all play a role in facilitation of the excitability of spinal motoneurons by locally applied 5-HT. Differentiation between these subtypes of receptor awaits the development of more completely selective agonists and antagonists.
Jackson
D A
DA
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164.
White
S R
SR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007478:Iontophoresis; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008839:Microelectrodes; D009046:Motor Neurons / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; D012701:Serotonin; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D011224:Prazosin; D008784:Methysergide