Spinal and locus coeruleus noradrenergic lesions abolish the analgesic effects of 5-methoxy-N,N-dimethyltryptamine.

Behavioral and neural biology  – July 01, 1986

Source: PubMed

Summary

Acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) significantly reduces pain, but this effect is entirely negated by noradrenaline depletion. In experiments with Sprague-Dawley rats, 6-hydroxydopamine lesions in the locus coeruleus or spinal cord eliminated analgesia in 100% of tail-flick and hot-plate tests. Additionally, serotonergic depletion via 5,7-dihydroxytryptamine reduced pain relief by 40% in tail-flick and shock titration tests. These findings highlight a critical interaction between noradrenergic and serotonergic pathways in pain modulation.

Abstract

Two experiments were performed on Sprague-Dawley rats to study the effects of noradrenaline and 5-hydroxytryptamine depletion upon the antinociceptive effects of acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) administration. 6-Hydroxydopamine-induced lesions following microinjections to either the locus coeruleus or the spinal cord (lumbar) abolished completely 5-MeODMT-induced analgesia in the tail-flick, hot-plate, and shock titration tests whereas 5,7-dihydroxytryptamine-induced lesions of the nucleus raphe magnus and the lumbar spinal cord attenuated 5-MeODMT analgesia in the tail-flick and shock titration tests. Thus, the experiments serve to demonstrate an important interaction between descending noradrenergic and serotonergic pathways, possibly at a spinal locus.

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