Absence of 6-hydroxydopamine in the rat brain after treatment with stimulants and other dopaminergic agents: a mass fragmentographic study.

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  • Additional Information
    • Source:
      Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print Cited Medium: Print ISSN: 0022-3042 (Print) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
      Original Publication: New York : Raven Press
    • Subject Terms:
      Brain/*metabolism ; Dopamine Agents/*pharmacology ; Oxidopamine/*metabolism; Animals ; Carbidopa/pharmacology ; Corpus Striatum/metabolism ; Dihydroxyphenylalanine/analogs & derivatives ; Dihydroxyphenylalanine/chemistry ; Dihydroxyphenylalanine/pharmacology ; Drug Combinations ; Drug Stability ; Frontal Lobe/metabolism ; Gas Chromatography-Mass Spectrometry ; Injections, Intraventricular ; Male ; Oxidopamine/chemistry ; Oxidopamine/pharmacology ; Pargyline/pharmacology ; Rats ; Rats, Sprague-Dawley ; Stimulation, Chemical
    • Abstract:
      Formation of 6-hydroxydopamine (6-OHDA) from dopamine has been hypothesized to mediate neurodegeneration induced by some psychostimulants. Although the emergence of a 6-OHDA-like substance was reported in the striatum of methamphetamine-treated rats, this substance has not been identified by a direct approach. We used mass fragmentography to search for 6-OHDA in the rat frontal cortex and striatum after the administration of a number of drugs including 3,4-dihydroxyphenyl-L-alanine, methamphetamine, amphetamine, and cocaine, all of which increase synaptic dopamine. No 6-OHDA was detected after the acute systemic administration of these agents. Intraventricular administration of 6-OHDA (10 micrograms/rat) produced measurable concentrations of 6-OHDA that were higher in the striatum than in the frontal cortex. Intraventricular administration of 2,4,5-trihydroxyphenyl-D,L-alanine (6-OHDOPA; 10 micrograms/rat) produced similar concentrations of 6-OHDA in both regions. Pargyline, but not carbidopa (alpha-methyl-dopa-hydrazine), enhanced the effect of intraperitoneal 6-OHDOPA administration (80 mg/kg). We conclude that (1) 6-OHDOPA can cross the blood-brain barrier and is converted to 6-OHDA in the brain, (2) 6-OHDA is a substrate for monoamine oxidase(s) and therefore a search for its purported deaminated metabolite is warranted, and (3) acute treatment with the above stimulants either does not lead to the formation of 6-OHDA or produces concentrations below the detection limit of the assay (< 34 pg/mg of protein).
    • Accession Number:
      0 (Dopamine Agents)
      0 (Drug Combinations)
      21373-30-8 (6-hydroxydopa)
      63-84-3 (Dihydroxyphenylalanine)
      8HW4YBZ748 (Oxidopamine)
      9MV14S8G3E (Pargyline)
      MNX7R8C5VO (Carbidopa)
    • Publication Date:
      Date Created: 19931001 Date Completed: 19931021 Latest Revision: 20190630
    • Publication Date:
      20231215
    • Accession Number:
      10.1111/j.1471-4159.1993.tb13630.x
    • Accession Number:
      8104232