Brain research
April 29, 1985
T Archer, B G Minor, C Post
37 citations
Depleting noradrenaline in rats reversed the pain-relieving effect of the 5-HT agonist 5-MeO-DMT, turning it into pain hypersensitivity in a shock-titration test and completely blocking its antinociceptive effects in hot-plate and tail-flick tests. Depleting serotonin stores did not alter the analgesia caused by 5-MeO-DMT. The results provide strong evidence that central noradrenaline depletion affects the analgesic action of the 5-HT agonist, suggesting an important tonic influence of the noradrenaline system on the descending spinal 5-HT pathway.
Physiology & behavior
January 1, 1987
T Archer, E Arweström, B G Minor et al.
32 citations
In 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.
Neuroscience letters
December 23, 1982
T Archer, S O Ogren, S B Ross
24 citations
Drugs that increase serotonin activity—5-MeO-DMT, fenfluramine, and PCA—impair rats' ability to retain fear, as shown by reduced immobility after inescapable shocks. Long-term PCA treatment, which depletes central serotonin neurons, completely blocked the retention impairment caused by acute PCA and fenfluramine, and partially blocked the deficit from 5-MeO-DMT. However, serotonin depletion via PCPA did not block these effects, suggesting different serotonin stores are involved. These findings underscore the role of the ascending serotonin pathway in aversive conditioning in rats.
Acta pharmacologica et toxicologica
August 1, 1986
W Danysz, B G Minor, C Post et al.
20 citations
Chronic treatment with the antidepressant desipramine consistently reduced pain relief caused by 5-MeODMT in rats across several pain tests, while chronic amitriptyline sometimes increased that pain relief. Acute antidepressant treatment raised shock thresholds in rats not given 5-MeODMT, but effects differed from chronic treatment. The findings highlight that acute and chronic antidepressant effects on pain perception are distinct.
British journal of pharmacology
October 1, 1986
T Archer, W Danysz, G Jonsson et al.
16 citations
In rats, drugs that block alpha-2 adrenoceptors (yohimbine and phentolamine) injected into the spinal cord prevented or reduced the pain-relieving effects of a serotonin-like drug (5-MeODMT) in three different pain tests (hot-plate, tail-flick, and shock titration). A different blocker (prazosin) reduced the pain relief in two of the tests but not the third. Yohimbine alone lowered pain thresholds in a dose-dependent way. The results indicate that alpha-2 adrenoceptors interact with serotonin-induced pain relief at the spinal level.
The Journal of pharmacy and pharmacology
September 1, 1985
T Archer, B Tandberg, L Rènyi et al.
8 citations
Repeated administration of drugs that increase tryptaminergic neurotransmission blocked the effects of an acute injection of 5-MeODMT on postdecapitation convulsions in rats. Zimelidine, fluoxetine, amiflamine, and alpha-ethyltryptamine given orally over 10 days substantially blocked the increase in latency and duration of convulsions caused by 5-MeODMT, while alaproclate, clorgyline, and pargyline caused a lesser blockade. Repeated 5-MeODMT administration completely blocked the acute effects. These findings suggest down-regulation of serotonin receptors mediating the convulsion response and offer a simple model for studying receptor sensitivity changes at the spinal level.
Journal of neural transmission
January 1, 1988
B G Minor, M L Persson, C Post et al.
7 citations
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.
Behavioral and neural biology
July 1, 1986
W Danysz, G Jonsson, B G Minor et al.
6 citations
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.
Acta pharmacologica et toxicologica
September 1, 1984
T Archer, B Tandberg
6 citations
An injection of the serotonin agonist drug 5-methoxy-N,N-dimethyltryptamine in rats lengthened both the time until and the duration of convulsions triggered by decapitation, starting at a dose of 0.5 mg/kg. Pretreatment with the serotonin antagonist methergoline (2.0 mg/kg) partially blocked these effects. Long-term administration of p-chloroamphetamine or p-chlorophenylalanine did not counteract the drug's effects but independently prolonged convulsion duration. The authors suggest the method may be useful for studying serotonin receptor mechanisms.
Pharmacology & toxicology
January 1, 1987
T Archer
2 citations
Several compounds that block serotonin (5-HT) receptors were tested for their ability to counteract changes in postdecapitation convulsions (PDCs) caused by 5-MeODMT, a serotonin agonist. Mianserin, methergoline, cinanserin, and methysergide substantially reduced the 5-MeODMT-induced prolongation of the time before convulsions began (latency) and, to a lesser extent, the duration of convulsions. Their effectiveness ranked mianserin > cinanserin > methysergide > methergoline. Pirenperone (a 5-HT2 antagonist) and pimozide (a dopamine antagonist) did not block these effects. When given alone, mianserin, methergoline, cinanserin, and methysergide prolonged convulsion duration but not latency; pirenperone prolonged both; pimozide had no effect. This suggests that 5-MeODMT's effects on PDCs are mediated through 5-HT1 receptors, offering a reliable model for studying spinal function.