Dopaminergic neurotoxicity of cyanide: neurochemical, histological, and behavioral characterization.
Previous reports have shown that dopamine (DA) is depleted in the brains of animals treated with cyanide. To develop a model for studying the mechanisms of cyanide-induced changes in dopaminergic systems, mice were treated with cyanide (KCN, 6 mg/kg, sc) twice a day for 7 days and 16 hr after the last dose neurochemical, histological, or behavioral parameters were evaluated. DA levels in KCN-treated animals decreased in the striatum (41%), hippocampus (30%), and cerebral cortex (13%) as compared to saline-treated controls. In striatal and hippocampal tissues, but not in cerebral cortex, malondialdehyde levels increased 43 and 57%, respectively, as compared to controls, indicating that peroxidation of lipids occurred in these brain areas. Over 30% of the treated mice exhibited decreased locomotor activity and akinesia, which were suppressed by l-DOPA (100 mg/kg, ip). Tyrosine hydroxylase (TH) immunohistochemical examination of brains from cyanide-treated animals showed a reduced number of TH-positive cells in substantia nigra, indicating a loss of dopaminergic neurons. In contrast, acute cyanide (KCN, 6 mg/kg, sc) did not produce significant neurochemical or behavioral changes. Under these treatment conditions, cyanide produces a central dopaminergic toxicity which is characterized by decreased DA levels in select brain areas, impaired locomotor activity, and neuronal damage.
Kanthasamy
A G
AG
Department of Pharmacology and Toxicology, Purdue University, West Lafayette, Indiana 47907-1334.
Borowitz
J L
JL
Pavlakovic
G
G
Isom
G E
GE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D011190:Potassium Cyanide / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects
D015102:3,4-Dihydroxyphenylacetic Acid; D008315:Malondialdehyde; D014446:Tyrosine 3-Monooxygenase; D011190:Potassium Cyanide; D004298:Dopamine