Effect of 6-hydroxydopamine on brain norepinephrine and dopamine evidence for selective degeneration of catecholamine neurons

Abstract

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.

Fig. 1

Effect of 6-hydroxydopamine (6-OH-DA) on brain norepinephrine, 5-hydroxytryptamine and dopamine. Animals pretreated with pargyline received 200 μg of 6-hydroxydopamine intracisternally and were killed 21 days later. Each bar is the mean of 8 to 16 animals. Vertical bars indicate S.E.M. *, P < .001.

Fig. 2

Effect of 6-hydroxydopamine on brain norepinephrine (A) and dopamine (B) at various times after injection. Animals pretreated with pargyline received 200 μg of 6-hydroxydopamine and were killed at various times after this injection. Control values for norepinephrine and dopamine were 605 ± 12.2 and 1136 ± 58 mμg, respectively. Vertical bars indicate S.E.M. Each value represents six to eight determinations.

Fig. 3

Effect of pargyline on brain depletion of catecholamines (A and B) by 6-hydroxydopamine. Various doses of 6-hydroxydopamine were administered intracisternally to animals with or without pargyline pretreatment. Animals, were sacrificed 16 or 21 days later. Stippled area indicates control values ±S.E.M. of 20 animals. Each point indicates the mean of 6 to 12 animals; vertical bar indicates the S.E.M. *, P < .01.

Fig. 4

Effect of 6-hydroxydopamine (6-0H-DA) on the metabolism of intracisternally administered norepinephrine-H³. Two doses of 6-hydroxydopamine (200 μg) were administered: the first was injected to pargyline-treated animals 21 days before sacrifice and the second dose was administered 7 days after the first dose. Animals were sacrificed 2 hours after the intracisternal injection of H³-norepinephrine (5 μc). Results are expressed as percentage of control ±S.E.M. Each value represents the mean of at least 10 determinations. Control mean norepinephrine-H³ = 1000 mμc/brain; normetanephrine-H³ = 136 mμc/brain; H³-deaminated catechols = 3 μc/brain; labeled O-methylated deaminated metabolites = 700 mμc/brain. *, P < .001; **, P < .05.