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抗精神病药物诱导大鼠僵住症潜力的评估:对一种新型商用半自动仪器的评价

Evaluation of the potential of antipsychotic agents to induce catalepsy in rats: assessment of a new, commercially available, semi-automated instrument.

作者信息

Bricker Barbara, Sampson Dinithia, Ablordeppey Seth Y

机构信息

Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.

出版信息

Pharmacol Biochem Behav. 2014 May;120:109-16. doi: 10.1016/j.pbb.2014.02.013. Epub 2014 Feb 21.

Abstract

Haloperidol induced catalepsy was determined using the classic bar test and a new MED Associates Catalepsy Test Chamber instrument. The dose that produced an adverse effect in 50% of rats (AED50) for haloperidol was calculated using the instrument data as 0.29 mg/kg. Hand scoring of the video recordings gave AED50 values of 0.30 and 0.31 mg/kg, both well within the 95% CL of the instrument data. Clozapine was also evaluated and catalepsy was not detected up to 40 mg/kg. No significant difference was found between the instrument and hand scoring data. The instrument was useful for testing haloperidol and clozapine, relieving much of the tedium and variability experienced without its use. It was especially valuable at measuring shorter time periods, where the researcher cannot react as quickly. Finally, olanzapine was also evaluated. However, clenched forepaws and hind paws prevented the use of the instrument alone at higher doses. A backup stopwatch was used for the bar test in these cases. Some of the advantages and limitations are discussed. Results are also compared to the crossed-legs position (CLP) test for all three antipsychotics. While haloperidol gave similar results at all concentrations tested, clozapine deviated significantly at the highest dose (40 mg/kg) displaying catalepsy in the CLP test but not in the bar test. Olanzapine displayed catalepsy in rats significantly different from vehicle at 40 mg/kg in both the bar and CLP tests. However, the CLP test may be more suited to compounds with gripping problems which prevent the consistent grasping of the bar. Overall, the instrument was found to be a useful aid in conducting the bar test for catalepsy. The CLP test was found to complement the bar test under certain conditions and could provide additional data that might be missed by the bar test for compounds producing grasping problems.

摘要

使用经典的杆式试验和新型MED Associates僵住症测试箱仪器来测定氟哌啶醇诱导的僵住症。利用该仪器数据计算出氟哌啶醇对50%大鼠产生不良反应的剂量(AED50)为0.29mg/kg。对视频记录进行人工评分得出的AED50值为0.30和0.31mg/kg,均在仪器数据的95%置信区间内。还对氯氮平进行了评估,在高达40mg/kg的剂量下未检测到僵住症。仪器数据和人工评分数据之间未发现显著差异。该仪器对于测试氟哌啶醇和氯氮平很有用,减少了不使用它时所经历的许多乏味和变异性。在测量较短时间段时它特别有价值,因为研究人员无法那么快做出反应。最后,也对奥氮平进行了评估。然而,前爪和后爪紧握使得在较高剂量下无法单独使用该仪器。在这些情况下,杆式试验使用了备用秒表。讨论了一些优点和局限性。还将所有三种抗精神病药物的结果与盘腿姿势(CLP)试验进行了比较。虽然氟哌啶醇在所有测试浓度下都给出了相似的结果,但氯氮平在最高剂量(40mg/kg)时出现了显著偏差,在CLP试验中显示出僵住症,而在杆式试验中未显示。在杆式试验和CLP试验中,奥氮平在40mg/kg时在大鼠中显示出僵住症,与赋形剂有显著差异。然而,CLP试验可能更适合于存在抓握问题、无法持续抓住杆的化合物。总体而言,发现该仪器对进行杆式僵住症试验很有帮助。发现CLP试验在某些条件下可补充杆式试验,并可为杆式试验可能遗漏的、存在抓握问题的化合物提供额外数据。

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