NORADRENALINE DEPLETION EXACERBATES MPTP-INDUCED STRIATAL DOPAMINE LOSS IN MICE

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