In vivo analysis of hydrogen peroxide and lipid radicals in the striatum of rats under long-term administration of a neuroleptic.
It has been hypothesized that free radicals play a causative role in tardive dyskinesia, which is an inveterate movement disorder caused by chronic administration of neuroleptics. To verify this hypothesis, rats were reared while being regularly treated with water containing a neuroleptic, haloperidol (HPD), for 1 year (HPD group). The changes in the striatal hydrogen peroxide content of the rats in the HPD and control groups were measured by using a Pt-disk microelectrode while the animals were in a freely moving state following intraperitoneal administration of HPD (HPD challenge). We also performed electron spin resonance (ESR) detection of lipid radicals in the striatum before the HPD challenge. HPD challenge led to significant elevation of the intrastriatal hydrogen peroxide in all animals, but the elevation in the HPD group was smaller than that in the control group. However, in the HPD group, marked ESR signals of intrastriatal lipid radicals were observed. We think that these results support the hypothesis on the role of free radicals in tardive dyskinesia.
Yokoyama
H
H
Institute for Life Support Technology Yamagata Technopolis Foundation, Japan.
Kasai
N
N
Ueda
Y
Y
Niwa
R
R
Konaka
R
R
Mori
N
N
Tsuchihashi
N
N
Matsue
T
T
Ohya-Nishiguchi
H
H
Kamada
H
H
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006220:Haloperidol / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D050356:Lipid Metabolism; D008297:Male; D009589:Nitrogen Oxides / Q000378:metabolism; D011725:Pyridines; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage; D019097:Spin Trapping
D014150:Antipsychotic Agents; D005609:Free Radicals; D009589:Nitrogen Oxides; D011725:Pyridines; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D012965:Sodium Chloride; D006861:Hydrogen Peroxide; D006220:Haloperidol