Opposing influences of D-1 and D-2 dopamine receptors activation on morphine-induced antinociception.

Subcutaneous (s.c.) injection of morphine (3-9 mg/kg) to mice induces a dose-related antinociceptive effect in the tail-flick test. In animals treated with different doses of apomorphine (0.1-3 mg/kg, s.c.) the antinociceptive effect of morphine changed; low doses of apomorphine were found to potentiate, whereas higher doses of the drug decreased the antinociception induced by morphine. Intraperitoneal (i.p.) injection of the D-2 agonist bromocriptine (0.5-2 mg/kg) increased the antinociceptive action of morphine dose-dependently. This potentiation was decreased in animals pretreated with sulpiride. The D-1 agonist SKF 38393 (4-12 mg/kg, i.p.) caused a reduction of morphine antinociception in a dose-dependent manner. The inhibitory effect of SKF 38393 was decreased in animals pretreated with SCH 23390. Theophylline (12.5-50 mg/kg, i.p.) pretreatment of animals decreased the morphine antinociception. Single administration of SCH 23390 increased the base line latency, while bromocriptine, SKF 38393, sulpiride, theophylline or apomorphine did not change the latency in the tail-flick test. It may be postulated that D-1 receptor activation decreases, while D-2 receptor stimulation increases the antinociceptive effects of morphine. Whether the effects of D-1 and D-2 receptors are mediated through the changes in cAMP levels remains to be clarified.