Neonatal 6-hydroxydopamine administration to mice is fatal.
Depletion of dopamine in adult rats by treatment with the neurotoxin 6-hydroxydopamine (6-OHDA) causes severe deficits in feeding, drinking, and movement that often lead to death. However, when neonatal rats are treated similarly, they survive normally, suggesting that compensatory adaptation to dopamine depletion occurs. In contrast, dopamine-deficient mice that have a selective genetic deficiency in dopamine production die 2-4 weeks after birth. Thus, we tested the hypothesis that killing dopaminergic neurons with 6-OHDA might promote survival of dopamine-deficient mice. Body weights, motor coordination, catecholamine levels, and survival were monitored for several weeks after bilateral administrations of 6-OHDA to 3-day-old mice. Some treated mice were raised in a heated chamber to help them conserve energy. The results demonstrate that regardless of genotype or environmental temperature, bilateral neonatal 6-OHDA lesions are lethal to mice.
Brot
Michelle D
MD
Department of Orthodontics, University of Washington, Seattle, Wash 98195-7370, USA.
Szczypka
Mark S
MS
Reavell
Randy
R
Marck
Brett T
BT
Matsumoto
Alvin M
AM
Palmiter
Richard D
RD
D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D013696:Temperature; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D018663:Adrenergic Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine