Sacavage Steve, Patel Hiren, Zielinski Mike, Acker Jeneane, Phillips Austin G, Raffa Robert B, Rawls Scott M
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
Neurosci Lett. 2008 Jul 4;439(1):84-8. doi: 10.1016/j.neulet.2008.04.086. Epub 2008 Apr 30.
Planarians display a concentration-related reduction in locomotor activity following their spontaneous withdrawal from opioids, cannabinoids, stimulants and benzodiazepines. This suggests that planarians display a withdrawal-like behavior that can be quantified as a reduction in locomotor activity. Because withdrawal-like behavior in previous studies has been quantified only following the cessation of a 60-min drug exposure, it is unclear whether the withdrawal response varies with drug exposure duration. Therefore, the goal of this study is to determine if the duration of drug exposure (0, 5, 15, 30, 45, 60min and 24h) to three different drugs - methamphetamine, cocaine and caffeine - affects the magnitude of withdrawal-like behavior (i.e., reduced locomotor activity) in planarians. Experiments revealed that methamphetamine (10microM) produced significant withdrawal-like behavior regardless of the exposure time (P<0.05). An exposure time of only 5min resulted in a significant reduction in locomotor activity. The peak effect, although occurring following a 24-h exposure, was only slightly greater than that caused by a 30-min exposure. For cocaine (10microM), a longer exposure time (15min) was required for the manifestation of significant withdrawal-like behavior. The peak cocaine effect was observed following a 24-h exposure. Caffeine (10microM) did not produce significant changes in locomotor activity during withdrawal or alter locomotor activity during acute exposure. The present results suggest that the magnitude of withdrawal-like behavior in planarians is dependent on both the duration and type of drug exposure, and that planarians do not display withdrawal to caffeine.
涡虫在自发戒断阿片类药物、大麻素、兴奋剂和苯二氮卓类药物后,其运动活性会出现与浓度相关的降低。这表明涡虫表现出一种类似戒断的行为,这种行为可以通过运动活性的降低来量化。由于在先前的研究中,类似戒断的行为仅在60分钟药物暴露停止后才被量化,因此尚不清楚戒断反应是否会随药物暴露持续时间而变化。因此,本研究的目的是确定三种不同药物——甲基苯丙胺、可卡因和咖啡因——的药物暴露持续时间(0、5、15、30、45、60分钟和24小时)是否会影响涡虫中类似戒断行为的程度(即运动活性降低)。实验表明,无论暴露时间如何,甲基苯丙胺(10微摩尔)都会产生显著的类似戒断行为(P<0.05)。仅5分钟的暴露时间就导致运动活性显著降低。尽管在24小时暴露后出现峰值效应,但仅略大于30分钟暴露所引起的效应。对于可卡因(10微摩尔),需要更长的暴露时间(15分钟)才能表现出显著的类似戒断行为。在24小时暴露后观察到可卡因的峰值效应。咖啡因(10微摩尔)在戒断期间未引起运动活性的显著变化,也未改变急性暴露期间的运动活性。目前的结果表明,涡虫中类似戒断行为的程度取决于药物暴露的持续时间和类型,并且涡虫对咖啡因不表现出戒断反应。