期刊
BEHAVIOURAL BRAIN RESEARCH
卷 194, 期 1, 页码 44-51出版社
ELSEVIER
DOI: 10.1016/j.bbr.2008.06.021
关键词
Parkinson's disease; dopamine agonists; cabergoline; pramipexole; levodopa; levodopa-induced dyskinesias; 6-OHDA-lesioned rat
资金
- National Parkinson Foundation (Miami, Fla.)
- Agencia Nacional para la promocion de la Ciencia y la Tecnologia [PICT 2002 11063]
- Universidad de Buenos Aires [UBACYT M037]
Levodopa-induced dyskinesias are one of the major limiting side effects encountered in the treatment of Parkinson's disease. Dopamine agonists of the D2 family are less prone to induce these abnormal involuntary movements (AIMs), and in some instances it has been proposed that they could counteract them once already established. As differences in the plasma half-life of a given DA agonist could be related with a greater or lesser propensity to induce or to counteract AIMS, we compared the effects of two D2 agonists (cabergoline and pramipexole) with different half-lives, and levodopa, at doses producing similar improvement in purposeful forelimb use, in rats with severe nigrostriatal lesion, previously sensitized to levodopa. The same therapeutic regime was subsequently used in pharmacologically naive rats. We found that: (i) prior induction of AIMS by levodopa administration primes rats for the occurrence of AIMS during mono-therapy with pramipexole (but not with cabergoline); (ii)an intervening period of D2 agonist monotherapy does not modify the severity of AIMS induced by subsequent mono-therapy with levodopa; iii. de novo treatment with D2 agonists is associated with a lower risk of AIMS (regardless of the severity of the lesion) and does not modify AIMS during subsequent mono-therapy with levodopa. An unexpected finding was that prior levodopa therapy sensitized rats to the therapeutic effects of D2 agonists given in monotherapy. In summary, the use of the rat with nigrostriatal lesion to model relevant therapeutic conditions does not support that D2 agonists prevent the development of AIMS during subsequent levodopa monotherapy or can revert the dysfunction underlying it. (C) 2008 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据