Modeling tardive dyskinesia: predictive 5-HT2C receptor antagonist treatment.
Modeling tardive dyskinesia: predictive 5-HT2C receptor antagonist treatment.
复制标题
迟发性运动障碍建模：预测性 5-HT2C 受体拮抗剂治疗。
DOI：
10.1007/bf03033481
复制
发表时间：
2007
影响因子：
3.7
通讯作者：
Brus,Ryszard
中科院分区：
文献类型：
--
作者：
Kostrzewa,RichardM;Huang,Nuo-Yu;Kostrzewa,JohnP;Nowak,Przemyslaw;Brus,Ryszard
迟发性运动障碍（TD）是一种由经典抗精神病药物长期治疗产生的运动障碍，通常被认为是多巴胺（DA）系统的障碍，因为经典抗精神病药物是有效的DA d2受体阻滞剂。此外，已知急性DA - 1拮拮剂治疗大鼠会产生空洞咀嚼运动（VCMs），这是一种类似于口腔运动障碍的行为特征，在大多数TD病例中非常突出。在本文中，我们概述了一系列新的动物模型的研究，在该模型中，新生儿6-羟多巴胺（6-OHDA）诱导黑质纹状体DA纤维的破坏产生DA d1受体超敏。在5-羟色胺受体受损的大鼠中，额外产生了超敏感性，事实上5-羟色胺受体拮抗剂减弱了用氟哌啶醇治疗一年的DA - d16损伤大鼠，vcm的数量增加了2倍（与用氟哌啶醇治疗的完整大鼠相比）；这种高频率的vcm在停止氟哌啶醇治疗后持续6个多月。在这个阶段，5- ht2受体拮抗剂，而不是DA d1受体拮抗剂，可以减弱vcm的发生率。这一系列的发现暗示了5-HT神经元在TD中的表型，并促进了5- ht2受体拮抗剂，更具体地说，5- ht2受体拮抗剂，作为人类TD的合理治疗方法。
Tardive dyskinesia (TD), a movement disorder produced by long-term treatment with a classical antipsychotic drug, is generally considered to be a disorder of dopamine (DA) systems, since classical antipsychotics are potent DA D2receptor blockers. Also, acute DA D1agonist treatment of rats is known to produce vacuous chewing movements (VCMs), a behavioral feature resembling the oral dyskinesia that is so prominent in most instances of TD. In this paper we outline a series of studies in a new animal model of TD in which DA D1receptor supersensitivity was produced by neonatal 6-hydroxydopamine (6-OHDA) -induced destruction of nigrostriatal DA fibers. In rats so-lesioned 5-HT receptor supersensitivity is additionally produced, and in fact 5-HT receptor antagonists attenuate enhanced DA D16-lesioned rats treated with haloperidol for one year, there is a 2-fold increase in numbers of VCMs (versusintact rats treated with haloperidol); and this high frequency of VCMs persists for more than 6 months after discontinuing haloperidol treatment. During this stage, 5-HT2receptor antagonists, but not DA D1receptor antagonists, attenuate the incidence of VCMs. This series of findings implicates the 5-HT neuronal phenotype in TD, and promotes 5-HT2receptor antagonists, more specifically 5-HT2Creceptor antagonists, as a rational treatment approach for TD in humans.