Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice.

Injection of C57Bl/6 mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 4 x 10 mg/kg i.p. over 8 h) resulted in a partial (40%) striatal dopamine depletion at 7 days post-drug. Pretreatment with the selective noradrenergic neurotoxin N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine (DSP-4; 40 mg/kg i.p.), while having no effect per se on striatal dopamine levels, exacerbated the MPTP-induced dopamine deficit to 60%. Results support the hypothesis that damage to the locus coeruleus-noradrenergic system, by removing a facilitatory influence on the nigrostriatal dopamine system, interferes with the ability of the nigrostriatal pathway to compensate for or recover from injury.