Effects of the experimental diabetes on dopamine D1 receptor-mediated locomotor-enhancing activity in mice

The effects of diabetes on the dopamine-related locomotor-enhancing activities were studied in mice. Although spontaneous locomotor activity in diabetic mice was significantly greater than that in nondiabetic mice, the locomotor-enhancing effects of methamphetamine (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.) and SKF82958 (1 mg/kg, s.c.), a selective dopamine D1-receptor agonist, in diabetic mice were significantly lower than those in nondiabetic mice. When dopamine level in the whole brain was reduced by pretreatment with 6-hydroxydopamine (6-OHDA), spontaneous locomotor activity was significantly reduced in both nondiabetic and diabetic mice. There was no significant difference in the total spontaneous locomotor activity counts within 3 h between 6-OHDA-treated nondiabetic and 6-OHDA-treated diabetic mice. Furthermore, the locomotor-enhancing effect of SKF82958 in 6-OHDA-treated diabetic mice was also significantly lower than that in 6-OHDA-treated nondiabetic mice. In a binding assay, the Bmax values of [3H]SCH23390 binding to whole-brain membranes of diabetic mice were significantly lower than those in nondiabetic mice. However, there was no significant difference in the Kd values between nondiabetic and diabetic mice. These results suggest that the decreased density of dopamine D1 receptors in diabetic mice may result in hyporesponsiveness to dopamine-related locomotor enhancement.