Potentiation of morphine analgesia by d-amphetamine is mediated by norepinephrine and not dopamine

Morphine will raise the threshold for escape from aversive electrical stimulation delivered to the mesencephalic reticular formation and this effect is potentiated by d-amphetamine. In order to study the roles which dopamine and norepinephrine play in modulating opiate analgesia, the effects of amfonelic acid, an indirect dopamine agonist, and nisoxetine, a selective norepinephrine reuptake blocker, were determined alone and in combination with morphine using this supraspinal model of analgesia. Amfonelic acid alone produced hyperalgesia and completely antagonized the analgesic effect of morphine. Nisoxetine had no effect by itself, however, it potentiated the analgesic effect of morphine when the two drugs were administered concomitantly. These findings suggest that norepinephrine and not dopamine plays a predominant role in the potentiation of opiate analgesia by d-amphetamine.