Involvement of dopamine D2 receptor-mediated functions in the modulation of morphine-induced antinociception in diabetic mouse

Abstract

The effects of the dopamine agonists and antagonists on morphine-induced antinociception in diabetic mice were studied. The antinociceptive effect of morphine (5 mg/kg, s.c.) in diabetic mice was significantly less than that in non-diabetic mice. The antinociceptive effect of morphine in diabetic mice, but not that in non-diabetic mice, was significantly enhanced following pretreatment with sulpiride, a selective dopamine D2 antagonist, (30 mg/kg, s.c.). Pretreatment with quinpirole, a selective dopamine D2 agonist, (100 nmol, i.c.v.), markedly increased the antinociceptive effect of morphine in diabetic mice, but not in non-diabetic mice. There was no significant difference in the antinociceptive effect of morphine (5 mg/kg, s.c.) between the quinpirole-treated diabetic mice and saline-treated non-diabetic mice. A higher dose of quinpirole (300 nmol, i.c.v.) had no significant effect on morphine-induced antinociception in diabetic mice. On the other hand, the antinociceptive effect of morphine was significantly reduced by pretreatment with quinpirole (300 nmol, i.c.v.) in non-diabetic mice. Quinpirole (100 and 300 nmol, i.c.v.) dose-dependently increased total locomotor activity in non-diabetic mice. In contrast, a lower dose of quinpirole (100 nmol, i.c.v.) significantly reduced spontaneous locomotor activity in diabetic mice, while a higher dose of quinpirole had no significant effect on the spontaneous locomotor activity. The dopamine turnover ratio in the limbic forebrain and midbrain in diabetic mice were significantly greater than those in non-diabetic mice. When mice were pretreated with quinpirole (100 and 300 nmol, i.c.v), this enhanced dopamine turnover ratio was not observed in either the limbic forebrain or the midbrain of diabetic mice. These findings suggest that the attenuation of morphine-induced antinociception and dopamine D2 receptor-mediated function in diabetic mice may somehow be related.