Different role of 5-HT1A and 5-HT2 receptors in spinal cord in the control of nociceptive responsiveness.
The effects of the 5-hydroxytryptamine type-2 (5-HT2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT1A agonist (+)-8-hydroxy-2-(di-n-propylamino)-tetralin [(+)-8-OH-DPAT] on nociceptive responsiveness were compared in mice. Intrathecal administration of DOI (5-20 micrograms) produced a dose-dependent behavioural syndrome, consisting of biting or licking, directed towards the caudal part of the body and reciprocal hindlimb scratching. However, (+)-8-OH-DPAT (5-20 micrograms) did not produce the biting and scratching behaviour. The response to DOI (20 micrograms) was reversed by treatment with the substance P receptor antagonist, [D-Arg1, D-Trp7,9, Leu11]-SP (Spantide) (5 micrograms). The tail-flick reflex was markedly depressed 5-20 min after administration of (+)-8-OH-DPAT; DOI did not change the tail-flick reflex after 5 min but significantly inhibited the reflex response 10-20 min after injection. The data show that stimulation of 5-HT2 receptors, but not 5-HT1A receptors, induced a behavioural syndrome, which may reflect activation of nociceptive pathways. The tail-flick reflex was more markedly inhibited by stimulation of 5-HT1A than 5-HT2 receptors. Accordingly, 5-HT2 and 5-HT1A receptors seem to have a different function in the modulation of nociceptive responsiveness in the mouse.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Hole
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000662:Amphetamines; D000700:Analgesics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D013373:Substance P; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C042867:spantide; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine