Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia.
Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD.
Abílio
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VC
Department of Pharmacology, Escola Paulista de Medicina/Universidade Federal de Sao Paulo, Edificio José Leal Prado-Rua Botucatu, 862 CEP 04023-062 Sao Paulo, SP, Brazil. vanabilio@uol.com.br
Silva
R H
RH
Carvalho
R C
RC
Grassl
C
C
Calzavara
M B
MB
Registro
S
S
D'Almeida
V
V
Ribeiro
R de A
Rde A
Frussa-Filho
R
R
D000375:Aging / Q000502:physiology*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000201:enzymology* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012110:Reserpine; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D012110:Reserpine; D002374:Catalase; D005979:Glutathione Peroxidase; D000640:Amitrole