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.
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.
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.