Estudo comportamental e bioquímico da coadministração de lítio e tamoxifeno em modelo animal de mania

• Ano de defesa: 2014
• Autor(a) principal: Armani, Fernanda [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: mania; modelo animal lítio tamoxifeno; terapia adjunta; camundongos
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1469280; http://repositorio.unifesp.br/handle/11600/48688

Therapeutic management of Bipolar Disorder (BD) targets the rapid suppression of symptoms and prevention of recurrence by treatment interruption, evoking the importance of adherence. These challenges may be addressed by using drugs with different profiles of efficacy and tolerability, such as lithium and tamoxifen. Thus, we assessed the ability of maintaining and interrupting treatment with lithium and/or tamoxifen in reverting and preventing recurrence of hyperactivity as mania-like parameter. We also investigated adherence to this combined treatment through the reduction of adverse effects of one agent by adding another. Then, C57BL/6J mice were randomly distributed to receive saline or methamphetamine (induction agent) within the first 3 days. Between the 4th and 8th days they were treated with vehicle or lithium ´Reversion Treatment. From 9th to 13th days, they were assigned to continue or interrupt lithium and/or tamoxifen ? Maintenance Treatment. Locomotion frequencies were assessed in automated activity chambers. In study 2, naive mice were subjected to conditioning treatment with saline, or saline or lithium followed by post-treatment with saline, lithium and/or tamoxifen. The conditioning scores were determined by place conditioning box. Our findings demonstrated that the progressively increased activity induced by methamphetamine was reversed by day 3 of lithium and tamoxifen coadministration and by day 5 of lithium or tamoxifen administered separately. Subsequently, the recurrence of hyperactivity occurred after 1 day of treatment discontinuation with lithium and after 2 days of interruption with tamoxifen alone or in combination with lithium. These effects were not due to increased lithium bioavailability by tamoxifen. Furthermore, tamoxifen was not able to bock acquisition or evocation of lithium-induced place aversion. Taken together, our findings suggest that the superior speed of action for remission and delay at reappearance of manic symptoms by lithium and tamoxifen combined treatment could prevent relapse and benefit patients affected by TB. However, a potential greater adherence of this therapy might not be based on the reduction of the adverse effects of lithium by tamoxifen.