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.
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Michael F. Sugrue (1979) studied this question.
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