Dunne Fergal, O'Halloran Ambrose, Kelly John P
Department of Pharmacology and Therapeutics, University Road, NUI, Galway, Ireland.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Oct 1;31(7):1456-63. doi: 10.1016/j.pnpbp.2007.06.023. Epub 2007 Jul 3.
The advent of automated locomotor activity methodologies has been extremely useful in removing the subjectivity and bias out of measuring this parameter in rodents. However, many of these behavioural studies are still conducted in novel environments, rather than in ones that the animals are familiar with, such as their home cage. The purpose of the present series of experiments was to develop an automated home cage tracking (HCT) profile using EthoVision software and assessing the acute effects of stimulant (amphetamine and methamphetamine, 0-5 mg/kg, sc) and sedative (diazepam, 0-20 mg/kg, sc and chlordiazepoxide, 0-50 mg/kg sc) drugs in this apparatus. Young adult male Sprague-Dawley rats were used, and the home cage locomotor activity was recorded for 11-60 min following administration (n=4 per group). For amphetamine and methamphetamine, a dose-dependent increase in home cage activity was evident for both drugs, with a plateau, followed by reduction at higher doses. Methamphetamine was more potent, whereas amphetamine produced greater maximal responses. Both diazepam and chlordiazepoxide dose-dependently reduced locomotor activity, with diazepam exhibiting a greater potency and having stronger sedative effects than chlordiazepoxide. Three doses of each drug were selected at the 31-40 min time period following administration, and compared to open field responses. Diazepam, chlordiazepoxide and amphetamine did not produce significant changes in the open field, whilst methamphetamine produced a significant increase in the 2.5 mg/kg group. In conclusion, these studies have successfully developed a sensitive HCT methodology that has been validated using drugs with stimulant and sedative properties in the same test conditions, with relatively small numbers of animals required to produce statistically significant results. It has proven superior to the open field investigations in allowing dose-response effects to be observed over a relatively short observation period (i.e. 10 min) for both stimulants and sedatives. In addition, the HCT system can determine differences in potency and efficacy between drugs of a similar chemical class.
自动运动活动方法的出现对于消除啮齿动物该参数测量中的主观性和偏差极为有用。然而，许多此类行为研究仍在新环境中进行，而非在动物熟悉的环境中，比如它们的饲养笼。本系列实验的目的是使用EthoVision软件开发一种自动饲养笼跟踪（HCT）模式，并评估兴奋剂（苯丙胺和甲基苯丙胺，0 - 5mg/kg，皮下注射）和镇静剂（地西泮，0 - 20mg/kg，皮下注射和氯氮卓，0 - 50mg/kg皮下注射）药物在此装置中的急性效应。使用年轻成年雄性斯普拉格 - 道利大鼠，给药后记录饲养笼运动活动11 - 60分钟（每组n = 4）。对于苯丙胺和甲基苯丙胺，两种药物在饲养笼中的活动均呈现剂量依赖性增加，达到平台期后，在更高剂量时下降。甲基苯丙胺效力更强，而苯丙胺产生更大的最大反应。地西泮和氯氮卓均剂量依赖性降低运动活动，地西泮效力更强，镇静作用比氯氮卓更强。在给药后31 - 40分钟时间段选择每种药物的三个剂量，并与旷场反应进行比较。地西泮、氯氮卓和苯丙胺在旷场中未产生显著变化，而甲基苯丙胺在2.5mg/kg组产生显著增加。总之，这些研究成功开发了一种灵敏的HCT方法，该方法已在相同测试条件下使用具有兴奋和镇静特性的药物进行验证，产生统计学显著结果所需动物数量相对较少。已证明其在允许在相对较短观察期（即10分钟）内观察到兴奋剂和镇静剂的剂量 - 反应效应方面优于旷场研究。此外，HCT系统可以确定相似化学类别的药物之间效力和效果的差异。
