(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion.
Physiology & behavior – January 01, 1987
Source: PubMed
Summary
The 5-HT agonists 8-OH-DPAT and 5-MeODMT significantly reduced pain in rats and mice, showing reliable analgesic effects across various tests like tail-flick and hot-plate. In experiments with 20 animals per treatment group, prior administration of the noradrenaline neurotoxin DSP4 completely negated these analgesic effects. Additionally, treatment with 6-hydroxydopamine reversed the pain relief from 8-OH-DPAT to hyperalgesia, highlighting a critical interaction between noradrenergic terminals and serotonergic receptors in managing spinal pain responses.
Abstract
In experiments with both rats and mice the 5-HT agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) were shown to produce reliable analgesic effects after acute administration (1 mg/kg SC) in the tail-flick, hot-plate and shock-titration tests of nociception. Prior treatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), systemically administered to both rats and mice abolished the analgesic effects of both the 5-HT agonist compounds in all the tests of nociception used. Intrathecal 6-hydroxydopamine (6-OHDA) treatment also abolished the analgesic effects of 8-OH-DPAT and 5-MeODMT; in the tail-flick test the analgesia induced by 8-OH-DPAT was reversed to an hyperalgesia. Biochemical analyses confirmed notable noradrenaline depletions in the spinal cord. It is concluded that an important interaction between presynaptic noradrenergic terminals and serotonergic receptor sites, possibly 5-HT1A, mediates spinal nociception processes.