Antinociception can be produced at the spinal level by activation of opioidergic, noradrenergic, and serotonergic systems. We tested the antinociceptive effects of combined activation of all three systems. Antinociception was assessed in the rat tail-flick test, and drugs were administered via an intrathecal catheter. Morphine, the norepinephrine uptake inhibitor desipramine, and serotonin produced antinociception of their own. The combination of subthreshold doses of morphine 1 �g and of desipramine 3 �g produced pronounced antinociception that was antagonized by yohimbine. The combination of subthreshold morphine with serotonin 50 �g or desipramine with serotonin caused only small antinociceptive effects. When morphine combined with desipramine was decreased to
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