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GABAa受体拮抗剂对小鼠药理学帕金森病模型运动行为的影响。

Effects of GABAa receptor antagonists on motor behavior in pharmacological Parkinson's disease model in mice.

作者信息

Mograbi Karla De Michelis, de Castro Ana Carolini Ferreira, de Oliveira Jainny Aniely Rocha, Sales Patrick Jean Barbosa, Covolan Luciene, Del Bel Eliane Aparecida, de Souza Albert Schiaveto

机构信息

Laboratory of Biophysiopharmacology, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil

Laboratory of Biophysiopharmacology, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.

出版信息

Physiol Rep. 2017 Mar;5(6). doi: 10.14814/phy2.13081.

Abstract

The aim of this study was to evaluate the effects of two gamma-amino butyric acid (GABA)a receptor antagonists on motor behavioral tasks in a pharmacological model of Parkinson disease (PD) in rodents. Ninety-six Swiss mice received intraperitoneal injection of Haloperidol (1 mg/kg) to block dopaminergic receptors. GABAa receptors antagonists Bicuculline (1 and 5 mg/kg) and Flumazenil (3 and 6 mg/kg) were used for the assessment of the interaction among these neurotransmitters, in this PD model. The motor behavior of the animals was evaluated in the catalepsy test (30, 60, and 90 min after drugs application), through open field test (after 60 min) and trough functional gait assessment (after 60 min). Both Bicuculline and Flumazenil were able to partially reverse catalepsy induced by Haloperidol. In the open field test, Haloperidol reduced the number of horizontal and vertical exploration of the animals, which was not reversed trough application of GABAa antagonists. Furthermore, the functional gait assessment was not sensitive enough to detect motor changes in this animal model of PD. There is an interaction between dopamine and GABA in the basal ganglia and the blocking GABAa receptors may have therapeutic potential in the treatment of PD.

摘要

本研究的目的是评估两种γ-氨基丁酸(GABA)A受体拮抗剂对啮齿动物帕金森病(PD)药理学模型中运动行为任务的影响。96只瑞士小鼠接受腹腔注射氟哌啶醇(1毫克/千克)以阻断多巴胺能受体。在该PD模型中,使用GABA A受体拮抗剂荷包牡丹碱(1和5毫克/千克)和氟马西尼(3和6毫克/千克)来评估这些神经递质之间的相互作用。在僵住试验(给药后30、60和90分钟)、旷场试验(60分钟后)和低谷功能步态评估(60分钟后)中评估动物的运动行为。荷包牡丹碱和氟马西尼均能够部分逆转氟哌啶醇诱导的僵住。在旷场试验中,氟哌啶醇减少了动物的水平和垂直探索次数,而通过应用GABA A拮抗剂并未逆转这一情况。此外,功能步态评估对检测该PD动物模型中的运动变化不够敏感。基底神经节中多巴胺和GABA之间存在相互作用,阻断GABA A受体可能在PD治疗中具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fd1/5371543/4a5d5d202cc4/PHY2-5-e13081-g001.jpg

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