Porsolt, 9(bis) Rue Henri Martin, 92100 Boulogne-Billancourt, France.
Pharmacol Biochem Behav. 2012 Jun;101(4):553-63. doi: 10.1016/j.pbb.2012.03.001. Epub 2012 Mar 9.
Preclinical testing requires rapid and reliable evaluation of the main in vivo effects of novel test substances usually in rodents. Nevertheless, the techniques primarily used up to now involve either automated measurement of motor activity or direct observation of behavioral effects by extensively trained investigators. The advantages of these approaches are respectively high-throughput and comprehensive behavioral assessment. Nevertheless, motor activity is only one aspect of animal behavior and it cannot predict the full neurobehavioral profile of a substance, whereas direct observation is time-consuming. There is thus a need for novel approaches that combine the advantages of both automatic detection and comprehensive behavioral analysis. In the present study, we used the LABORAS™ system to analyze motor and non-motor behavior in rats administered various stimulant substances with or without known psychotomimetic properties or abuse liability (amphetamine, cocaine dizocilpine (MK-801), ketamine, modafinil and nicotine). The data show that LABORAS™ clearly detects the stimulating effects on motor behaviors of amphetamine, cocaine, dizocilpine and ketamine in a dose- and time-dependent manner. Differential effects of these test substances on non-motor behaviors, such as grooming, eating and drinking could also be detected. Nicotine displayed only slight stimulating effects on locomotion, whereas modafinil was virtually without effect on the behaviors evaluated by the system. These data with different stimulant substances suggest that LABORAS™ presents an advantage over classical methods performing automated measurements restricted to locomotion. Furthermore, the procedure is considerably more rapid than behavioral observation procedures. Characterization of the behavioral profile of test substances using LABORAS™ should therefore accelerate preclinical studies. In addition, the multi-faceted parameters measured by LABORAS™ permit a more detailed comparison of the behavioral profiles of novel substances with standard reference substances, thereby providing important indicators for orienting further substance evaluation and supporting drug development.
临床前测试需要快速可靠地评估新型测试物质在通常在啮齿动物体内的主要体内效应。然而，迄今为止主要使用的技术要么涉及自动测量运动活动，要么通过经过广泛训练的研究人员直接观察行为效应。这些方法的优点分别是高通量和全面的行为评估。然而，运动活动只是动物行为的一个方面，它不能预测物质的完整神经行为特征，而直接观察则很耗时。因此，需要新的方法来结合自动检测和全面行为分析的优点。在本研究中，我们使用 LABORAS™ 系统分析了给予各种兴奋剂物质的大鼠的运动和非运动行为，这些物质具有或不具有已知的致幻作用或滥用倾向（安非他命、可卡因、地佐辛（MK-801）、氯胺酮、莫达非尼和尼古丁）。数据显示，LABORAS™ 以剂量和时间依赖的方式清楚地检测到安非他命、可卡因、地佐辛和氯胺酮对运动行为的刺激作用。还可以检测到这些测试物质对非运动行为（如梳理、进食和饮水）的不同影响。尼古丁对运动仅有轻微的刺激作用，而莫达非尼对系统评估的行为几乎没有影响。这些具有不同兴奋剂物质的数据表明，LABORAS™ 与仅执行自动测量限制在运动的经典方法相比具有优势。此外，该程序比行为观察程序快得多。使用 LABORAS™ 对测试物质的行为特征进行表征，因此应该会加速临床前研究。此外，LABORAS™ 测量的多方面参数允许更详细地比较新型物质与标准参考物质的行为特征，从而为进一步的物质评估提供重要指标，并支持药物开发。
