Differential roles of 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) 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-HT(1A) agonists, m-trifluoromethylphenyl- piperazine (TFMPP) and 7-trifluoromethy-4(4-methyl-1-piperazinyl)- pyrrolo(1,2-1a)quinoxaline (CGS 12066B), 5-HT(1B) agonists, and 5- carboxamidotryptamine (5-CT), a mixed 5-HT(1A) and 5HT(1B) 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-HT(1A) and 5-HT(1B) 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 facilitatory role of 5-HT(1A) receptor subtype on nociceptive responses and support the involvement of 5-HT(1B) receptor subtype in the antinociceptive action of serotonin.