Dose-related effects of continuous levodopa infusion in rats with unilateral lesions of the substantia nigra

摘要: Preclinical studies in rats have demonstrated markedly different effects of intermittent and continuous levodopa administration on many biochemical functional parameters yet the dose regimens employed not been fully evaluated. In this study, with unilateral 6-hydroxydopamine nigral lesions were administered (0-1200 mg/kg/day) benserazide (25 subcutaneously via osmotic minipump studied 20-22 h later for rotational behavior, striatal dopamine concentration, regional cerebral glucose utilization (RCGU). Levodopa infusion at 100 mg/kg/day resulted minimal rotation replacement but did increase RCGU subthalamic nucleus decrease lateral habenula, consistent a selective inhibition striatopallidal GABAergic (indirect output) pathway. significantly entopeduncular (EP) substantia nigra pars reticulata (SNr), as does acute injection (25-50 mg/kg), indicating that elicits only part spectrum metabolic elicited by injection. Higher doses (400-1200 moderate rates rotation, dose-dependent increases dopamine, increased EP SNr, activation striatonigral (direct two major output nuclei basal ganglia, 800 1200 reproduced levodopa. These results demonstrate, first time, distinct populations neurons which may be relevant to pathogenesis levodopa-induced dyskinesias Parkinson's disease. The partial indicate need caution interpretation prior dose.