The actions of 5-HT1 agonists and antagonists on nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies.
We have developed a technique which allows drugs to be microinjected intrathecally intrathecally in anaesthetised rats whilst single unit recordings are made from dorsal horn neurones. Using this technique together with recordings of tail flick latency (TFL) elicited from lightly anaesthetised rats we have found that the specific 5-HT1a agonist 8-OH DPAT (15, 150, 300 nmol) increases nociceptive responses recorded from single dorsal horn neurones and decreases TFL. The non-specific 5-HT1b agonist TFMPP (300 nmol) and the general 5-HT1 agonist 5-CT (0.3, 3.0, 30 nmol) both decreased nociceptive responses and has inconsistent effects on TFL. Intrathecally applied 5-HT (130, 260 nmol) generally reduced nociceptive neuronal responses and increased TFL. In a minority of experiments, however, 5-HT increased nociceptive responses and it is suggested that this effect is associated with activation of 5-HT1a receptors. Activity at 5-HT1b receptors has the effect of suppressing or reducing responsiveness. The increased responsiveness of dorsal horn neurones to noxious stimulation associated with activity at 5-HT1a receptors may be associated either with increases in receptive field size, promotion of spinal nocifensive reflexes or the facilitation of the rostral transmission to specific brainstem sites.
Department of Physiology, University of Wales, Cardiff, UK.
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Ali
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Wu
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Kozlov
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Barasi
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D013997:Time Factors
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine