Halladay Lindsay R, Iñiguez Sergio D, Furqan Faiza, Previte Matt C, Chisum Ashley M, Crawford Cynthia A
Department of Psychology, California State University, San Bernardino, CA 92407, USA.
Pharmacol Biochem Behav. 2009 Mar;92(1):190-6. doi: 10.1016/j.pbb.2008.11.011. Epub 2008 Dec 7.
The goal of this study was to determine if the exaggerated morphine-induced conditioned place preference (CPP) response seen in adult rats after preweanling methylphenidate exposure is unique to reward-mediated behaviors or is indicative of generalized changes in opioid-mediated behaviors. Rats were exposed to saline or methylphenidate (2.0 or 5.0 mg/kg) for 10 consecutive days starting on postnatal (PD) 11 with testing beginning on PD 60. In Experiment 1, morphine-induced (0, 2.5, 5.0 or 10.0 mg/kg) antinociception was assessed using the tail immersion and hot plate tasks. In Experiment 2, morphine-induced (0, 2.5, 5.0, or 10.0 mg/kg) hyperthermia and locomotor activity were measured. Morphine caused an increase in antinociception, with early methylphenidate (5.0 mg/kg) exposure potentiating the effects of 5.0 mg/kg morphine. Rectal temperatures were elevated after morphine, with the greatest increase occurring in male rats. Methylphenidate potentiated the hyperthermic effects of morphine (10.0 mg/kg) but only in males. Moderate doses (2.5 and 5.0 mg/kg) of morphine increased the locomotor activity of adult rats, while a higher dose (10.0 mg/kg) decreased locomotion. Interestingly, methylphenidate-pretreated females showed increased locomotor activity relative to controls. These results suggest that early methylphenidate exposure induces general changes in opioid system functioning that are not specific to reward-mediated behaviors.
本研究的目的是确定断奶前暴露于哌甲酯的成年大鼠中出现的夸大的吗啡诱导的条件性位置偏爱（CPP）反应是奖励介导行为所特有的，还是表明阿片类药物介导行为的普遍变化。从出生后（PD）11天开始，大鼠连续10天暴露于生理盐水或哌甲酯（2.0或5.0mg/kg），并于PD 60开始测试。在实验1中，使用尾浸法和热板任务评估吗啡诱导的（0、2.5、5.0或10.0mg/kg）抗伤害感受。在实验2中，测量吗啡诱导的（0、2.5、5.0或10.0mg/kg）体温过高和运动活动。吗啡引起抗伤害感受增加，早期暴露于哌甲酯（5.0mg/kg）可增强5.0mg/kg吗啡的作用。吗啡给药后直肠温度升高，雄性大鼠升高幅度最大。哌甲酯增强了吗啡（10.0mg/kg）的体温过高作用，但仅在雄性大鼠中。中等剂量（2.5和5.0mg/kg）的吗啡增加成年大鼠的运动活动，而较高剂量（10.0mg/kg）则降低运动。有趣的是，与对照组相比，经哌甲酯预处理的雌性大鼠运动活动增加。这些结果表明，早期暴露于哌甲酯会引起阿片系统功能的普遍变化，而不是特定于奖励介导的行为。
