Acute effects of 6-hydroxydopa on central monoaminergic neurons

The effect of 6-hydroxydopa (6-OHDOPA) on mouse whole brain monoamines was studied. It was shown that i.v. administration of a 100 mg/kg dose of 6-OHDOPA reduced whole brain norepinephrine (NE) by 35% after 24 hr, while dopamine (DA) levels were unchanged. With a 150 mg/kg dose whole brain NE levels were reduced by 70% after 3 hr and 55% after 24 hr; whole brain DA content was reduced by 15–20% at both time periods. The effects of 6-OHDOPA (150 mg/kg, i.v.) on NE depletion in the brain could be prevented by d- and l-amphetamine, desipramine and chlorpromazine. MK-486, a peripherally acting dopa decarboxylase inhibitor, potentiated NE depletion by 6-OHDOPA in the brain. While 6-OHDOPA had no effect on monoamine oxidase and choline acetylase activity in the ‘cortex’, brainstem and cerebellum, catechol-O-methyl transferase activity was reduced in the brainstem after 14 days and acetylcholinesterase activity was reduced in the ‘cortex’ after 2 and 14 days. It is concluded that moderate doses of 6-OHDOPA have a marked effect on central noradrenergic neurons, while dopaminergic neurons remain intact.