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

Abstract

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)