Modification of the effects of 7-OH-DPAT, a dopamine D3-receptor agonist, on morphine-induced hyperlocomotion by diabetes

We examined the effect of 7-OH-DPAT on spontaneous locomotor activity that is enhanced in diabetic mice. 7-OH-DPAT (0.1-30 mg/kg, s.c.) dose-dependently decreased the enhanced spontaneous locomotor activity in diabetic mice, but not in nondiabetic mice. When mice were pretreated with of 7-OK-DPAT (0.1 mg/kg), morphine-induced enhanced locomotor activity in nondiabetic mice, but not in diabetic mice, was significantly reduced. Furthermore, 7-OH-DPAT (0.1 mg/kg) significantly attenuated the morphine-induced increase in DA turnover in both nondiabetic and diabetic mice. However, DA turnover was significantly greater in diabetic mice than in nondiabetic mice. Thus, it is likely that the enhanced spontaneous locomotor activity in diabetic mice may be partially related to the down-regulation of D3-receptor-mediated modulation of dopamine release in the limbic area.