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.
Marien
M
M
Division Neurobiologie I, Centre de Recherche Pierre Fabre, Castres, France.
Briley
M
M
Colpaert
F
F
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism / Q000494:pharmacology*; D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism*
D018663:Adrenergic Agents; D001596:Benzylamines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine