Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

In rats, destroying spinal norepinephrine (NA) neurons with 6-hydroxydopamine eliminated the pain-relieving effect of the serotonin receptor agonist 5-MeODMT in three different pain tests. Replacing NA directly into the spinal cord restored the analgesic effect. Chemical analysis confirmed a 95% loss of NA in the spinal cord. Destroying serotonin neurons with 5,7-DHT reduced the analgesic effect in one test. The findings show that NA is necessary for 5-MeODMT to produce analgesia and further clarify how NA modulates serotonin-related pain relief.

Study at a glance

Abstract

Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.