Commissaris R L, Xie Z, Ninichuk P J, Markovska V L
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
Pharmacol Biochem Behav. 1996 Feb;53(2):369-77. doi: 10.1016/0091-3057(95)02036-5.
The present article describes a method for multiple within-day conflict testing to conduct drug treatment time course studies more efficiently. Groups of female Sprague-Dawley rats were trained for conflict testing in a standard one-session/day procedure [conditioned suppression of drinking (CSD)]. In this task, thirsty rats (24 h water-restricted) drink from a tube that is electrified only when a tone is on (approximately 20% of the 10-min session time). In Experiment 1 it was found that there was no significant variation in CSD conflict behavior when subjects were tested at 0600, 1200, or 1800 h using the traditional procedure of one test/day. In Experiment 2, subjects were assigned to treatment groups such that there were three 5-min test sessions per day and the test-retest interval was either 2, 4, or 6 h (centered around 1200 h). Test-retest intervals of 6 h (i.e., tests at 0600, 1200, and 1800 h) resulted in comparable levels of punished responding across the repeated within-day tests, whereas test-retest intervals of 2 h and, to a lesser extent 4 h, resulted in unequal within-day conflict behavior characterized by a greater number of shocks accepted and a greater volume of water consumed during the earliest test periods each day. In another group of rats, it was determined that conflict behavior sampled five times/day in 3-min sessions separated by a 3-h test-retest interval (i.e., tests at 0600, 0900, 1200, 1500, and 1800 h) also resulted in stable conflict behavior across the various within-day test periods. In Experiment 3, it was found that acute IP challenges with anticonflict treatments that exhibit either a long duration of action (phenobarbital: 40 mg/kg) or a significant delay to onset in addition to a long duration (MK-801: 0.20 mg/kg) yielded time course data comparable to those obtained using the traditional one test/day procedure. These findings indicate that the use of multiple within-day conflict testing can greatly increase the efficiency of these procedures, particularly when drug treatment timecourse information is desired.
本文描述了一种用于多次日内冲突测试的方法,以便更有效地进行药物治疗时间进程研究。将雌性Sprague-Dawley大鼠分组,按照标准的每日一次训练程序进行冲突测试[条件性饮水抑制(CSD)]。在该任务中,口渴的大鼠(禁水24小时)从一根仅在音调响起时(约占10分钟训练时间的20%)带电的管子饮水。在实验1中发现,当使用每日一次测试的传统程序在06:00、12:00或18:00对受试者进行测试时,CSD冲突行为没有显著差异。在实验2中,将受试者分配到各治疗组,使每天有三个5分钟的测试时段,重测间隔为2、4或6小时(以12:00为中心)。6小时的重测间隔(即06:00、12:00和18:00进行测试)在重复的日内测试中导致了相当水平的受罚反应,而2小时的重测间隔以及在较小程度上4小时的重测间隔,导致了日内冲突行为不均等,其特征是在每天最早的测试时段接受的电击次数更多,饮水量更大。在另一组大鼠中,确定每天在3分钟的时段内进行5次冲突行为采样,重测间隔为3小时(即06:00、09:00、12:00、15:00和18:00进行测试),在不同的日内测试时段也产生了稳定的冲突行为。在实验3中发现,对具有长作用持续时间(苯巴比妥:40mg/kg)或除长作用持续时间外还有显著起效延迟(MK-801:0.20mg/kg)的抗冲突治疗进行急性腹腔注射挑战,得到的时间进程数据与使用传统的每日一次测试程序获得的数据相当。这些发现表明,使用多次日内冲突测试可以大大提高这些程序的效率,特别是在需要药物治疗时间进程信息时。