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, SC), cocaine (20 mg/kg, SC) and SKF82958 (1 mg/kg, SC), a selective dopamine D-1-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. fn a binding assay, the B-max values of [H-3]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 K-d values between nondiabetic and diabetic mice. These results suggest that the decreased density of dopamine D-1 receptors in diabetic mice may result in hyporesponsiveness to dopamine-related locomotor enhancement. (C) 1998 Elsevier Science Inc.