Perry Jennifer L, Stairs Dustin J, Bardo Michael T
Division of Pharmacology and Toxicology, Minneapolis Medical Research Foundation, S-3 Laboratories, 860, 914 South 8th Street, Minneapolis, MN 55404, United States.
Behav Brain Res. 2008 Nov 3;193(1):48-54. doi: 10.1016/j.bbr.2008.04.019. Epub 2008 May 1.
Individual differences in impulsive choice and rearing in differential environments are factors that predict vulnerability to drug abuse. The present study determined if rearing influences impulsive choice, and if d-amphetamine or methylphenidate alters impulsive choice in differentially reared rats. Male Sprague-Dawley rats were raised from 21 days of age in either an enriched condition (EC) or an isolated condition (IC) and were tested as young adults on an adjusting delay task. In this task, two levers were available and a response on one lever yielded one 45mg food pellet immediately, whereas a response on the other yielded three pellets after an adjusting delay. The delay was initially set at 6s, and it decreased or increased by 1s following responses on the immediate or delayed levers, respectively. A mean adjusted delay (MAD) was calculated upon completion of each daily session, and it served as the quantitative measure of impulsivity. Once MADs stabilized, rats were injected with saline, d-amphetamine (0.5, 1.0, or 2.0mg/kg, s.c.), or methylphenidate (2.5, 5.0, or 10.0mg/kg, s.c.) 15min prior to adjusting delay sessions. EC rats had higher baseline MADs (were less impulsive) than IC rats. Additionally, administration of d-amphetamine, but not methylphenidate, dose-dependently increased impulsive choice (decreased MADs) in EC rats. In IC rats, d-amphetamine and methylphenidate dose-dependently decreased impulsivity (increased MADs). These results indicate that rearing environment influences impulsive choice and moderates the effect of psychostimulants on impulsive choice. Specifically, psychostimulants may decrease environment-dependent impulsive choice in individuals with high levels of impulsivity (e.g., those with ADHD), whereas they may increase impulsive choice in individuals with low levels of impulsivity.
冲动选择的个体差异以及在不同环境中的饲养方式是预测药物滥用易感性的因素。本研究确定了饲养方式是否会影响冲动选择，以及右旋苯丙胺或哌甲酯是否会改变不同饲养条件下大鼠的冲动选择。雄性斯普拉格-道利大鼠从21日龄起分别饲养在丰富环境（EC）或隔离环境（IC）中，并在成年后接受调整延迟任务测试。在该任务中，有两个杠杆可供操作，对一个杠杆的反应会立即产生一粒45毫克的食物颗粒，而对另一个杠杆的反应会在调整延迟后产生三粒。延迟最初设定为6秒，根据对即时或延迟杠杆的反应分别减少或增加1秒。每天的实验结束后计算平均调整延迟（MAD），它作为冲动性的定量指标。一旦MAD稳定，在调整延迟实验前15分钟给大鼠注射生理盐水、右旋苯丙胺（0.5、1.0或2.0毫克/千克，皮下注射）或哌甲酯（2.5、5.0或10.0毫克/千克，皮下注射）。EC大鼠的基线MAD较高（冲动性较低），高于IC大鼠。此外，右旋苯丙胺而非哌甲酯的给药剂量依赖性地增加了EC大鼠的冲动选择（降低了MAD）。在IC大鼠中，右旋苯丙胺和哌甲酯剂量依赖性地降低了冲动性（增加了MAD）。这些结果表明饲养环境会影响冲动选择，并调节精神兴奋剂对冲动选择的作用。具体而言，精神兴奋剂可能会降低高冲动性个体（如患有注意力缺陷多动障碍者）中与环境相关的冲动选择，而在低冲动性个体中可能会增加冲动选择。
