The effect of arsenic trioxide on brain monoamine metabolism and locomotor activity of mice.
The arsenic trioxide (AsT) content, and monoamine levels in the cerebral cortex, hippocampus, hypothalamus and corpus striatum were determined in mice administered AsT (3 and 10 mg/kg) for 14 days. The vertical and horizontal motor activity was also examined. The AsT content in discrete brain areas differed but was clearly dose-dependent. Metabolites of norepinephrine and dopamine increased in the cerebral cortex, hippocampus and hypothalamus and decreased in the corpus striatum in AsT-treated mice. Metabolites of 5-hydroxytryptamine increased in all the discrete brain areas. The vertical and horizontal motor activity was increased by AsT at 3 mg/kg and decreased by AsT at 10 mg/kg. These results show that AsT modifies CNS metabolism and function at low doses. AsT penetrates the blood-brain barrier to cause these effects.
Itoh
T
T
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
Zhang
Y F
YF
Murai
S
S
Saito
H
H
Nagahama
H
H
Miyate
H
H
Saito
Y
Y
Abe
E
E
D000284:Administration, Oral; D000818:Animals; D001151:Arsenic / Q000032:analysis / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010087:Oxides
D001152:Arsenicals; D010087:Oxides; D001151:Arsenic; D000077237:Arsenic Trioxide