Elevated striatal dopamine levels following administration of D-DOPA and its α-keto acid metabolite DHPPA: Behavioral and physiological studies in vivo in the rat

Timothy Brannan, Alla Prikhojan, Melvin D. Yahr

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The D stereoisomer of dihydroxyphenyl alanine (D-DOPA) and its α-keto acid metabolite 3,4-dihydroxyphenylpyruvic acid (DHPPA), when infused into the striatum, significantly increased in vivo extracellular dopamine levels. Following D-DOPA administration, the cumulative increase in dopamine levels was 30% of the increase following L-DOPA; following DHPPA it was 11% that of L-DOPA. Rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra demonstrated brisk contralateral turning following each compound. The turning, however, was delayed by 10-20 min and total turning was 40% less following D-DOPA and 57% less following DHPPA than it was following L-DOPA. These data indicate that exogenously administered D-DOPA can be metabolized in vivo within the brain to dopamine and suggest this may occur via a transamination pathway in which DHPPA is an intermediary metabolite. The possible relevance of these findings to the treatment of Parkinson's disease is discussed.

Original languageEnglish
Pages (from-to)165-168
Number of pages4
JournalBrain Research
Volume718
Issue number1-2
DOIs
StatePublished - Apr 29 1996

Keywords

  • Catecholamine metabolism
  • Cerebral microdialysis
  • D-DOPA
  • Dihydroxyphenylpyruvic acid
  • L-DOPA
  • Parkinson's disease

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