Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice.
The modulatory effect of spinal serotonin (5-HT)1 receptors on nociception was studied in mice. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, putative 5-HT1A agonists, m-trifluoromethylphenyl-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-1a)quinoxaline (CGS 12066B), 5-HT1B agonists, and 5-carboxamidotryptamine (5-CT), a mixed 5-HT1A and 5HT1B agonist, were used. Intrathecal administration of 8-OH-DPAT, buspirone and 5-CT (1-12 nmol/mouse) significantly facilitated the tail-flick reflex, whereas TFMPP and CGS 12066B prolonged tail-flick latency. When administered i.t. after s.c. pretreatment (25 min) with morphine sulfate, 8-OH-DPAT, buspirone and 5-CT shifted the morphine sulfate dose-response curve 3- to 5-fold to the right. Spiperone, propranolol and pindolol (mixed 5-HT1A and 5-HT1B antagonists) effectively reversed both the tail-flick facilitation and the antagonistic effect on morphine sulfate-induced antinociception produced by 8-OH-DPAT and 5-CT. In addition, simultaneous i.t. administration of 8-OH-DPAT with substance P or N-methyl-D-aspartic acid decreased biting but increased scratching behavior, an effect which is also blocked by the 5-HT1 antagonists. These results confirm and extend other reports on the facilitory role of 5-HT1A receptor subtype on nociceptive responses and support the involvement of 5-HT1B receptor subtype in the antinociceptive action of serotonin.
Alhaider
A A
AA
Department of Pharmacology, University of Minnesota, Minneapolis.
Wilcox
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GL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D013373:Substance P; D016202:N-Methylaspartate; D009020:Morphine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D002065:Buspirone