ON THE ROLE OF 5‐HYDROXYTRYPTAMINE IN DRUG‐INDUCED ANTINOCICEPTION

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Abstract
The effects of four specific inhibitors of 5‐hydroxytryptamine (5‐HT) uptake on morphine‐, methadone‐ or pethidine‐induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55°C) reaction times. The effect of the compounds on the uptake of [3H]‐5‐HT into rat whole brain synaptosomes was also investigated. Pretreatment with Org 6582, citalopram, zimelidine or femoxetine at doses devoid of antinociceptive activity potentiated morphine‐ but not methadone‐ or pethidine‐induced antinociception. A temporal correlation existed between the ability of Org 6582 to potentiate morphine‐induced antinociception and to block synaptosomal [3H]‐5‐HT uptake. 5‐HT plays a critical role in the antinociceptive effect of morphine but not of methadone or pethidine.

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