Efeitos dos neurolépticos atípicos ziprasidona e amisulprida em modelos animais de discinesia tardia

• Ano de defesa: 2009
• Autor(a) principal: Carvalho, Rita de Cassia [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Discinesia Orofacial; Neurolépticos; Dopamina; Modelos Animais
• Link de acesso: https://repositorio.unifesp.br/handle/11600/9430

Tardive dyskinesia - the main side effect of long-term treatment with typical neuroleptics - has been related to nigrostriatal dopaminergic supersensitivity. Treatment with atypical neuroleptics is associated with a decreased risk for development of tardive dyskinesia. The aim of the present study was to verify the effects of several doses the atypical neuroleptics ziprasidone (antagonist 5-HT2 and D2) and amisulpride (antagonist D2) on the development of orofacial dyskinesia per se, or induced by reserpine or haloperidol in mice (two animal models of tardive dyskinesia). In addition, we also verified a possible association between these effects and the development of nigrostriatal dopaminergic supersensitivity (evaluated by an increase in stereotyped behavior induced by a dopaminergic agonist). Opposite to reserpine and haloperidol, ziprasidone and amisulpride treatments were not able to induce either orofacial dyskinesia or nigrostriatal dopaminergic supersensitivity. Acute administration of these neuroleptics inhibited reserpine- and haloperidol-induced orofacial dyskinesia. Concomitant treatment with ziprasidone (but not amisulpride) impaired the development of reserpine- and haloperidol-induced orofacial dyskinesias but not the dopaminergic supersensitivity induced by these drugs. Finally, these effects are not related to inespecific changes on motor activity. Our results strengthen the alleged lower risk of tardive dyskinesia presented by atypical neuroleptics. More importantly, the antidyskinetic property of ziprasidone supports the potential therapeutic use of some atypical neuroleptics to prevent the development of tardive dyskinesia.