On the role of 5-hydroxytryptamine in drug-induced antinociception.
1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brain synaptosomes was also investigated. 2. Pretreatment with Org 6582, citalopram, zimelidine or femoxetine at doses devoid of antinociceptive activity potentiated morphine- but not methadone- or pethidine-induced antinociception. 3. A temporal correlation existed between the ability of Org 6582 to potentiate morphine-induced antinociception and to block synaptosomal [3H]-5-HT uptake. 4. 5-HT plays a critical role in the antinociceptive effect of morphine but not of methadone or pethidine.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D000700:Analgesics; D012702:Serotonin Antagonists; D012701:Serotonin; D009020:Morphine