Analgesia induced by 5-hydroxytryptamine receptor agonists is blocked or reversed by noradrenaline-depletion in rats.
The antinociceptive effect of acute administration of 5-HT receptor agonists and agents releasing 5-HT from neuronal terminals was studied in rats by using the hot-plate, tail-flick and shock-titration tests. Noradrenaline depletion by the noradrenaline-neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine hydrochloride (DSP4, 2 X 50 mg/kg) blocked the analgesia induced by the 5-hydroxytryptamine (5-HT) receptor agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and quipazine, as well as that induced by acute release of 5-HT by p-chloroamphetamine (PCA) and increased 5-HT synthesis by 5-hydroxytryptophan (5-HTP). Analgesia in the tail-flick test was partly blocked by both methergoline and mianserin, whereas the analgesic effects of 5-MeODMT in the hot-plate and shock-titration tests were unaffected by the 5-HT antagonists. In the shock-titration test it was found that the DSP4-pretreated animals were made hyperalgesic by acute 5-MeODMT, and this hyperalgesia was blocked by both mianserin and methergoline, implying that this effect was 5-HT receptor mediated. It is therefore concluded that a functional central noradrenergic system is required for eliciting 5-HT receptor mediated analgesia, and that these interactions, at least in part, are probably spinally located.
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000627:therapeutic use; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011814:Quipazine / Q000627:therapeutic use; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D010133:p-Chloroamphetamine / Q000627:therapeutic use
D000700:Analgesics; D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D011814:Quipazine; D010133:p-Chloroamphetamine; D006916:5-Hydroxytryptophan; D009638:Norepinephrine