Persistent depletion of striatal dopamine in mice by m-hydroxy-MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused marked depletion of dopamine and of its two metabolites, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid) one week after the last of four daily s.c. injections (20 mg/kg) in mice. Norepinephrine concentration in the frontal cortex was also decreased. m-Hydroxy-MPTP at a higher dose (80 mg/kg s.c.) caused a similar degree of depletion of dopamine and its metabolites in striatum and of norepinephrine in frontal cortex. p-Hydroxy-MPTP and o-hydroxy-MPTP (both at 80 mg/kg s.c.) caused no significant change in striatal dopamine or in cortical norepinephrine concentrations and had little or no effect on the dopamine metabolites. The m-hydroxy analog increases the list of MPTP-like compounds known to cause persistent depletion of striatal dopamine, and the positional isomers of this compound illustrate the strict structural dependency of this effect.