NOREPINEPHRINE LOSS EXACERBATES METHAMPHETAMINE-INDUCED STRIATAL DOPAMINE DEPLETION IN MICE

Evidence is accumulating that norepinephrine depletion enhances the ne urotoxic effect of the parkinsonism inducing neurotoxin 1-methyl-4-phe nyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we investigated w hether norepinephrine loss potentiates methamphetamine-induced striata l dopamine depletion. Injection of C57BL/6N mice with methamphetamine (2 x 5 mg/kg i.p., at 2-h intervals) produced only a partial (50%) str iatal dopamine depletion 7 days after drug administration. Pretreatmen t with the selective noradrenergic neuro toxin N-(-2-chloroethyl)-N-et hyl-2-bromobenzylamine (DSP-4; 50 mg/kg i.p.) enhanced methamphetamine -induced striatal dopamine depletion by 86%, without decreasing striat al dopamine levels when injected alone. Our results extend previous fi ndings obtained with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2 ,3,6-tetrahydropyridine in DSP-4-pretreated mice.