(+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion.
T Archer, E Arweström, B G Minor, M L Persson, C Post, E Sundström, G Jonsson
Physiology & behavior January 1, 1987 DOI: 10.1016/0031-9384(87)90350-7 via PubMed
Summary
AI-generated from the abstractIn rats and mice, two drugs that activate serotonin receptors (8-OH-DPAT and 5-MeODMT) reliably produced pain relief in three different tests (tail-flick, hot-plate, and shock-titration). However, when the animals were pretreated with a toxin that destroys noradrenaline neurons (DSP4) given systemically, or with 6-hydroxydopamine injected directly into the spinal cord, the pain-relieving effects of both drugs were eliminated. In the tail-flick test, 8-OH-DPAT actually caused increased pain sensitivity after spinal cord noradrenaline depletion. Biochemical measurements confirmed that the toxins severely reduced noradrenaline in the spinal cord. The findings suggest that the pain relief from these serotonin drugs depends on intact noradrenaline nerve endings in the spinal cord, pointing to a critical interaction between noradrenaline and serotonin systems in spinal pain processing.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats and mice |
| Interventions | 8-OH-DPAT 5-MeODMT DSP4 6-OHDA |
| Dose | 1 mg/kg SC |
| Citations | 32 |
| Key finding | The analgesic effects of the serotonin agonists 8-OH-DPAT and 5-MeODMT depend on intact spinal noradrenaline terminals, as depleting noradrenaline abolished or reversed pain relief. |
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.