EFFECT OF 6-HYDROXYDOPAMINE ON BRAIN NOREPINEPHRINE AND DOPAMINE: EVIDENCE FOR SELECTIVE DEGENERATION OF CATECHOLAMINE NEURONS
1 Departments of Psychiatry and Pharmacology and the Child Development Institute, University of North Carolina School of Medicine, Chapel Hill, North Carolina
After the intracisternal administration of 6-hydroxydopamine, brain levels of norepinephrine were reduced significantly with or without pargyline pretreatment. Depletion of dopamine in the central nervous system was found to be enhanced markedly by pargyline administration at higher dose levels of 6-hydroxydopamine. Brain serotonin concentrations were not altered. The effects of 6-hydroxydopamine were long-lasting with the depletion of brain amines persisting at 78 days. After norepinephrine-H3 intracisternally to animals treated with 6-hydroxydopamine, labeled norepinephrine uptake was diminished with a corresponding reduction of deaminated catechols and a marked increased in methylated amines. Tyrosine hydroxylase activity was found to be reduced in brainstem, caudate nucleus and whole brain in 6-hydroxydopamine-treated animals. Conversion of tyrosine-H3 to labeled norepinephrine and dopamine was also markedly diminished. The results support the view that 6-hydroxydopamine produces a "central sympathectomy" when introduced into cerebrospinal fluid.
Journal of Pharmacology And Experimental Therapeutics, Vol. 174, Issue 3, 413-420, 1970Copyright © 1970 by American Society for Pharmacology and Experimental Therapeutics