Studies on the formation of 6-hydroxydopamine in mouse brain after administration of 2,4,5-trihydroxyphenylalanine (6-hydroxyDOPA)

J. M. Evans, G. Cohen

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

2,4,5-Trihydroxyphenylalanine (6-OH-DOPA) destroys central and peripheral noradrenergic neurons, while sparing dopaminergic neurons. Previous studies indicate that 6-OH-DOPA toxicity is mediated by the formation of 6-hydroxydopamine. However, levels of 6-hydroxydopamine in brain following peripheral administration of 6-OH-DOPA have not been documented. In the current study, 6-OH-DOPA and 6-hydroxydopamine were measured in brain by HPLC with electrochemical detection after intraperitoneal injection of 6-OH-DOPA. when mice were injected with 100 mg 6-OH-DOPA/kg, 6-hydroxydopamine levels in the striatum were highest (1.9 μg/g) at 15 min and fell slowly to 24% of the peak value at 4 h. Experiments with reserpine indicated that the relative stability of 6-hydroxydopamine was largely dependent upon storage in synaptic vesicles. Reserpine (10 mg/kg) lowered striatal 6-hydroxydopamine levels to 21.6% of control (non-reserpine-treated) values at 1 h, and to 8.9% of control values at 4 h. Levels of 6-hydroxydopamine in the striatum at 1 h were increased 113% by pargyline (100 mg/kg), 145% by α-methyldopahydrazine (carbidopa; 25 mg/kg), and 261% by pargyline and carbidopa together. Levels of dopamine in the striatum were unchanged at 2.5 h after 200 mg 6-OH-DOPA/kg (with pargyline and 50 mg carbidopa/kg), whereas levels of norepinephrine in the frontal cortex fell by 77%. At the same time, 6-hydroxydopamine levels were 8.8-fold higher in the striatum (5.54 μg/g) than in the cortex (0.63 μg/g). The latter results show that the striatum is resistant to 6-OH-DOPA-mediated depletion of catecholamines even though the concentrations of 6-hydroxydopamine approach those of endogenous dopamine.

Original languageEnglish (US)
Pages (from-to)1461-1467
Number of pages7
JournalJournal of Neurochemistry
Volume52
Issue number5
StatePublished - 1989
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this