Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian rat

Neurosci Lett. 1996 Nov 8;218(3):145-8. doi: 10.1016/s0304-3940(96)13131-1.

Abstract

D-3,4-Dihydroxyphenylalanine (D-dopa) and L-3,4-dihydroxyphenylalanine (L-dopa) induced circling in rats with a unilateral 6-hydroxydopamine lesion of substantia nigra with similar potency. D-Dopa is not a substrate for aromatic L-amino acid decarboxylase, the enzyme which metabolizes L-dopa to dopamine. This raises the question of how D-dopa has behavioral effect. Two pathways have been suggested to result in conversion of D-dopa to L-dopa, one involving oxidation of D-dopa to dihydroxyphenylpyruvic acid (DHPPA) by D-amino acid oxidase, the other involving transamination of D-dopa to DHPPA. Here we show that sodium benzoate, an inhibitor of D-amino acid oxidase, blocks D-dopa-induced circling while having no effect on circling induced by L-dopa. The results suggest that conversion of D-dopa to L-dopa via DHPPA is highly dependent on oxidase activity and that sodium benzoate effectively inhibits this process in vivo in rat.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / adverse effects*
  • Antiparkinson Agents / metabolism
  • Behavior, Animal / drug effects
  • Benzoates / pharmacology*
  • Benzoic Acid
  • Carbidopa / pharmacology
  • Female
  • Food Preservatives / pharmacology*
  • Levodopa / adverse effects*
  • Levodopa / metabolism
  • Locomotion / drug effects
  • Parkinson Disease, Secondary / drug therapy*
  • Phenylpyruvic Acids / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antiparkinson Agents
  • Benzoates
  • Food Preservatives
  • Phenylpyruvic Acids
  • 3,4-dihydroxyphenylpyruvic acid
  • Levodopa
  • Benzoic Acid
  • Amino Acid Oxidoreductases
  • Carbidopa