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新型口服给药在抗精神病药物治疗动物模型中的应用。

Novel oral drug administration in an animal model of neuroleptic therapy.

作者信息

Schleimer Sonja B, Johnston Graham A R, Henderson Jasmine M

机构信息

Department of Pharmacology, School of Medical Sciences, Institute for Biomedical Research and Neuroscience Institute of Schizophrenia and Allied Disorders, Blackburn Bldg. DO6, The University of Sydney, NSW 2006, Australia.

出版信息

J Neurosci Methods. 2005 Aug 15;146(2):159-64. doi: 10.1016/j.jneumeth.2005.02.004.

Abstract

A novel method of oral drug administration was used in a neuroleptic animal study. Seventy male Sprague-Dawley rats were randomly subdivided into four groups, which were treated with clozapine, haloperidol, diazepam or a vehicle solution (5% sucrose solution). Oral drug treatment was achieved by training the rats to drink the drug of choice mixed with five percent sucrose or vehicle solution from a syringe. Within 3-4 weeks the haloperidol group developed vacuous chewing movement, which did not disappear with discontinuation of the drug. Significant weight gain was observed for all drug groups in relation to the control group, whereas only the diazepam group showed a significant increase in response latency on the disengage test of sensorimotor function, which disappeared with drug withdrawal. A novel means of testing the motivational status showed that all drug-treated groups engaged in eating chocolate before grooming (t=11.69, p<0.001), whereas the control group showed no specific tendency towards either task. Furthermore, there was a significant delay in grooming for the haloperidol group compared to the other drug groups and controls. In conclusion, a novel method of oral drug administration with minimum stress was introduced that was sufficient to cause the described changes in behavioural parameters. Additionally, the combination of tests used provided an efficient discrimination between the behavioural effects of clozapine, haloperidol and diazepam in rodents.

摘要

在一项抗精神病药物动物研究中采用了一种新型口服给药方法。70只雄性斯普拉格-道利大鼠被随机分为四组,分别用氯氮平、氟哌啶醇、地西泮或赋形剂溶液(5%蔗糖溶液)进行治疗。通过训练大鼠从注射器中饮用与5%蔗糖混合的所选药物或赋形剂溶液来实现口服药物治疗。在3至4周内,氟哌啶醇组出现了空嚼运动,停药后该运动并未消失。与对照组相比,所有药物组均观察到显著体重增加,而只有地西泮组在感觉运动功能脱离测试中的反应潜伏期显著增加,停药后该增加消失。一种测试动机状态的新方法表明,所有药物治疗组在梳理毛发前都会吃巧克力(t = 11.69,p < 0.001),而对照组在这两项任务上均无特定倾向。此外,与其他药物组和对照组相比,氟哌啶醇组在梳理毛发方面存在显著延迟。总之,引入了一种压力最小的新型口服给药方法,该方法足以引起行为参数的上述变化。此外,所使用的测试组合能够有效区分氯氮平、氟哌啶醇和地西泮对啮齿动物的行为影响。

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