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

Two experiments on rats show that depleting noradrenaline or serotonin in specific brain and spinal cord regions blocks or reduces pain relief from a drug called 5-MeODMT. Destroying noradrenaline-producing neurons in the locus coeruleus or spinal cord completely eliminated the drug's analgesic effect in three pain tests. Destroying serotonin-producing neurons in the nucleus raphe magnus or spinal cord only partly reduced the effect in two of the tests. The findings indicate that descending noradrenergic and serotonergic pathways interact, likely within the spinal cord, to produce this pain relief.

Study at a glance

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.