Effects of acute lethal cyanide intoxication on central dopaminergic pathways.
In rats treated with sodium cyanide (NaCN), 20 mg/kg intraperitoneally, the striatal dopamine (DA) level was decreased within 60 sec. compared to controls injected with NaCl 0.9%. Treatment with NaCN also increased the naturally occurring L-DOPA in the striatum, but not in the other brain regions studied. Decreased DA levels but increased L-DOPA accumulation were also seen in cyanide-treated animals after inhibition of neuronal L-aromatic amino decarboxylase. In rats given a non-lethal dose of NaCN, 2.5 mg/kg intraperitoneally, 30 min. before sacrifice and L-DOPA, 100 mg/kg intraperitoneally, 25 min. before sacrifice, regional L-DOPA levels were not significantly changed, but the striatal DA levels were diminished compared to controls. Decreased DA levels might indicate that cyanide inhibits the synthesis of brain DA. However, both increased L-DOPA and increased accumulation of L-DOPA after neuronal decarboxylase were observed after cyanide. Furthermore, we have earlier reported that lethal doses of NaCN decreased the DA metabolite HVA in the striatum but did not significantly change the oxidatively deaminated metabolite of DA, DOPAC. Inhibition of L-aromatic amino acid decarboxylase appears to play a minor role in causing decreased striatal DA levels. However, our findings might be compatible with cyanide-produced inhibition of the energy-demanding granular uptake and/or release of DA.
Cassel
G
G
Department of NBC Defence, National Defence Research Establishment, Umeå, Sweden.
Persson
S A
SA
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis*; D006834:Hydrazines / Q000008:administration & dosage; D007980:Levodopa / Q000008:administration & dosage / Q000032:analysis*; D008297:Male; D011041:Poisoning / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000008:administration & dosage / Q000506:poisoning*
D006834:Hydrazines; D007980:Levodopa; C004297:3-hydroxybenzylhydrazine; D012966:Sodium Cyanide; D004298:Dopamine