Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and locomotor activity in young adult rats.
Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and locomotor activity in young adult rats.
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DOI：
10.1016/j.pbb.2008.11.011
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Crawford CA
中科院分区：
文献类型：
--
作者：
Halladay LR;Iñiguez SD;Furqan F;Previte MC;Chisum AM;Crawford CA
本研究的目的是确定断奶前暴露于哌醋甲酯的成年大鼠中观察到的夸大的吗啡诱导的条件性位置偏好（CPP）反应是否是奖励介导的行为所特有的，还是表明阿片类药物介导的行为的普遍变化。从出生后 (PD) 11 开始，将大鼠连续 10 天暴露于盐水或哌醋甲酯（2.0 或 5.0 mg/kg），并从 PD 60 开始进行测试。在实验 1 中，使用尾部浸没和热板任务评估吗啡诱导的（0、2.5、5.0 或 10.0 mg/kg）抗伤害作用。在实验2中，测量吗啡诱导的（0、2.5、5.0或10.0mg/kg）高热和运动活动。吗啡引起镇痛作用增强，早期暴露哌醋甲酯（5.0 mg/kg）可增强 5.0 mg/kg 吗啡的作用。吗啡后直肠温度升高，其中雄性大鼠的升高幅度最大。哌醋甲酯增强吗啡（10.0 mg/kg）的热效应，但仅限于男性。中等剂量（2.5 和 5.0 毫克/千克）吗啡可增加成年大鼠的运动能力，而较高剂量（10.0 毫克/千克）则会降低运动能力。有趣的是，与对照组相比，经过哌醋甲酯预处理的雌性表现出运动活性增加。这些结果表明，早期暴露于哌醋甲酯会引起阿片类药物系统功能的一般变化，这些变化并非特定于奖励介导的行为。
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.
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