ENHANCEMENT BY 6-HYDROXYDOPAMINE OF THE EFFECTS OF DOPA UPON THE MOTOR ACTIVITY OF RATS

¹ Departments of Psychiatry and Neurology, Children's Hospital Medical Center; Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
² Departments of Psychiatry and Neurology, Children's Hospital Medical Center and Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The effect of 3,4-dihydroxyphenylalanine (dopa) on the motor activity of rats was determined two weeks after the intraventricular administration of 6-hydroxydopamine (250 µg, administered twice, 48 hours apart) or vehicle. After inhibition of peripheral decarboxylase activity, dopa had a dose-related biphasic effect on the motor activity of vehicle-treated rats. It decreased motor activity at low doses and increased motor activity at high doses. 6-Hydroxydopamine (6-HDA)-treated rats also showed a biphasic dose-response curve although the effects of dopa occurred at lower doses. The maximal increase in motor activity of 6-HDA-treated rats occurred within one hour of dopa administration and coincided with the maximal accumulation of both dopa and dopamine (DA) in whole brain. Inhibition of decarboxylase activity in the central nervous system prevented the accumulation of DA without altering the brain level of dopa and blocked the increase in motor activity. Althougim this suggests that DA formed from dopa mediates the effect of dopa in 6-HDA-treated rats, DA accumulation was never higher in these animals than in vehicle-treated rats, nor was there a higher level of DA in any brain region examined. It was found, however, that dopa increased motor activity as soon as 24 hours after the second dose of 6-HDA, at a time when the ³H-DA uptake was decreased by 50%. These results suggest that the enhanced effect of dopa in 6-HDA-treated rats is due to the production of a supersensitivity to catecholamines in the central nervous system of these animals.