REGIONAL EFFECTS OF L-DIHYDROXYPHENYLALANINE (L-DOPA) ON NOREPINEPHRINE METABOLISM IN RAT BRAIN

¹ Laboratory of Neuroendocrine Regulation and Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts

After 10 daily doses of L-dihydroxyphenylalanine (L-dopa) (100 mg/kg i.p.), rats received intracisternal tritiated norepinephrine (³H-NE) and a final dose of L-dopa five minutes later. They were killed at intervals during the next six hours and their brains were dissected into five regions (striatum, hypothalamus, brainstem, telencephalon and cerebellum) and assayed for NE, L-dopa, dopamine, ³H-NE and ³H-NE metabolites. L-Dopa caused decreases in the concentrations of O-methylated ³H-NE metabolites especially in the telencephalon, brainstem and cerebellum. As long as L-dopa was detectable in the brain, total NE pools were generally enlarged in these regions, as were dopamine levels in both the striatum and the rest of the brain. ³H-NE utilization was studied by examining three parameters: disappearance of ³H-NE, decline of ³H-NE specific activity and calculated turnover rate. Generally, these three parameters of ³H-NE kinetics were accelerated initially and then decelerated as a result of L-dopa treatment, with regional differences in magnitude and time course. In the hypothalamus, accelerated ³H-NE disappearance and turnover persisted throughout the period examined.