The effect of 6-hydroxydopamine on the antinociceptive action of morphine

Abstract

The role of brain catecholamines in the antinociceptive action of morphine was investigated. Intraventricular 6-hydroxydopamine which depleted brain noradrenaline in the rat had no effect on morphine's antinociceptive action but combined treatment with pargyline and 6-hydroxydopamine to further deplete brain dopamine potentiated morphine's action. It was also shown that when dopamine receptors were blocked, the antinociceptive action of morphine was potentiated whereas alpha- and beta-adrenoceptor antagonists had no effect. 6-Hydroxydopamine had two effects in mice tested on the hot-plate. It produced a hyperalgesia and antagonized the antinociceptive action of morphine. This antagonism of morphine appeared to be the result of the depletion of noradrenaline rather than dopamine. Intraventricular injection of both catecholamines restored the antinociceptive action of morphine in 6-hydroxydopamine-treated mice but dopamine was ineffective in the presence of a dopamine beta-hydroxylase inhibitor. It is suggested that the antinociceptive action of morphine is expressed by noradrenergic neurones in the mouse and by both noradrenergic and dopaminergic neurones in the rat.