dela Cruz Adriane M, Herin David V, Grady James J, Cunningham Kathryn A
Department of Pharmacology and Toxicology, Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas 77555-0615, USA.
Behav Pharmacol. 2009 Dec;20(8):720-30. doi: 10.1097/FBP.0b013e328333b266.
Only a subgroup of human drug users progress from initial drug taking to drug addiction. The learned associations between the effects of the drug and the environment in which it is experienced is an important aspect of the progression to continued drug taking and drug seeking. These associations can be modeled using the conditioned place preference (CPP) paradigm, although no current method of CPP analysis allows for the identification of within-group variability among subjects. In this study, we adapted a 'criterion' method of analysis to separate 'CPP expressing' from 'non-CPP expressing' rats to study more directly within-group variability in the CPP paradigm. Male Sprague-Dawley rats were conditioned with cocaine (5, 10, 20 mg/kg) or saline in an unbiased three-chamber CPP apparatus in either a single-trial or four-trial CPP procedure. A classification and regression tree analysis of time spent in the cocaine-paired chamber established a time of 324 s spent in the cocaine-paired chamber as the criterion for cocaine CPP expression. This criterion effectively discriminated control from cocaine-conditioned rats and was reliable for rats trained in both single trial and four-trial CPP procedures. The criterion method showed an enhanced ability to detect effective doses of cocaine in the single-trial CPP procedure and a blockade of CPP expression by MK 212 (0.125 mg/kg) treatment in a subgroup of rats. These data support the utility of the criterion analysis as an adjunct to traditional methods that compare group averages in CPP.
只有一部分人类吸毒者会从最初吸毒发展到药物成瘾。药物效果与用药环境之间形成的习得性关联是持续吸毒和觅药过程中的一个重要方面。这些关联可以使用条件性位置偏爱(CPP)范式来模拟,尽管目前的CPP分析方法都无法识别个体间的组内变异性。在本研究中,我们采用了一种“标准”分析方法,将“表达CPP”的大鼠与“不表达CPP”的大鼠区分开来,以便更直接地研究CPP范式中的组内变异性。将雄性Sprague-Dawley大鼠在无偏倚的三室CPP装置中,通过单次试验或四次试验的CPP程序,用可卡因(5、10、20mg/kg)或生理盐水进行条件化训练。对在与可卡因配对的实验箱中停留时间进行分类和回归树分析,确定在与可卡因配对的实验箱中停留324秒为可卡因CPP表达的标准。该标准有效地区分了对照组和可卡因条件化大鼠,并且对单次试验和四次试验CPP程序训练的大鼠都可靠。该标准方法在单次试验CPP程序中显示出更强的检测可卡因有效剂量的能力,以及在一组大鼠中通过MK 212(0.125mg/kg)处理对CPP表达的阻断作用。这些数据支持了标准分析作为传统CPP组均值比较方法辅助手段的实用性。