Acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine metabolism in mouse and rat striatum

J Pharm Pharmacol. 1985 Oct;37(10):707-11. doi: 10.1111/j.2042-7158.1985.tb04947.x.


Monoamines and metabolites in mouse striatum were measured at intervals (0-6 h) after injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 mg kg-1 subcutaneously). In addition, the accumulation of 3,4-dihydroxyphenylalanine (dopa), induced by inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), was assessed during every 15 min (0-135 min) after MPTP administration. The alterations induced by MPTP during the first hour after injection were a transient acceleration followed by a marked retardation of dopa synthesis, a decrease in 3,4-dihydroxyphenylacetic acid (DOPAC; -55%) and an increase in 3-methoxytyramine (3-MT; +400%). Between 60 and 75 min after administration, some dramatic changes took place: a 40% reduction of dopamine (DA), a marked additional increase in 3-MT (to 1300% of control) and an increase in homovanillic acid (HVA; +50%). The period after 75 min was characterized by a further depletion of DA, a decrease in 3-MT and a transient increase in HVA (max. 240% of control). Six hours after the administration, all concentrations of DA and its metabolites were subnormal, i.e. DA (30% of control), 3-MT (10%), DOPAC (10%) and HVA (65%). The MPTP-induced retardation of dopa synthesis was not antagonized by haloperidol or by reserpine pretreatment. MPTP (25 or 50 mg kg-1 s.c.) produced similar acute changes in the levels of DA and its metabolites in rat as in mouse striatum, though much less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 5-Hydroxytryptophan / metabolism
  • Animals
  • Corpus Striatum / metabolism*
  • Dihydroxyphenylalanine / metabolism
  • Dopamine / metabolism*
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Mice
  • Pyridines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Species Specificity
  • Time Factors
  • Tryptophan / metabolism
  • Tyrosine / metabolism


  • Pyridines
  • Tyrosine
  • Hydroxyindoleacetic Acid
  • Dihydroxyphenylalanine
  • Tryptophan
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 5-Hydroxytryptophan
  • Dopamine
  • Homovanillic Acid