Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats
Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats
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DOI：
10.1007/s00213-011-2564-1
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发表时间：
2012-05-01
影响因子：
3.4
通讯作者：
Cheong, Jae Hoon
中科院分区：
文献类型：
--
作者：
dela Pena, Ike;Yoon, Seo Young;Cheong, Jae Hoon
哌醋甲酯是一种精神兴奋剂，用于治疗注意力缺陷/多动症（ADHD）。该药物的长期影响尚不清楚，据推测，反复暴露可能产生药物依赖性。为了研究反复哌甲酯治疗对哌甲酯自我给药和恢复的影响，在最有效的ADHD动物模型，自发性高血压大鼠（SHR）和Wistar大鼠中，在实验之前，向大鼠腹膜内施用盐水或哌醋甲酯（2 mg/kg）14天。此后，评估了固定比例（FR 1和FR 3）和递进比例（PR）方案下静脉注射哌甲酯的反应。灭绝实验，以及测试，以确定腹腔内注射哌甲酯（2和5毫克/公斤），以恢复消失的药物寻求behaviors.Previous暴露于哌甲酯增强哌甲酯自我管理在Wistar大鼠，但不是在SHR（FR 3）的能力。哌甲酯预处理降低SHR对哌甲酯的反应，但不影响Wistar大鼠（PR）的自我给药行为。哌甲酯预暴露强烈恢复药物寻求行为在Wistar大鼠，但不是在SHR。反复哌甲酯治疗的对比效果哌甲酯自我管理和恢复在Wistar和SHR，和敏感性增加的Wistar大鼠品系哌甲酯的强化作用表明，“正常”的个人更有可能发展心理依赖的药物和经验复发。同时，哌甲酯的临床应用可能不会使ADHD患者产生药物依赖或复发。
Methylphenidate is a psychostimulant given for extended periods of time as a treatment of attention-deficit/hyperactivity disorder (ADHD). The long-term effects of the drug are not yet known, and it is speculated that repeated exposure may produce drug dependence.To investigate the effects of repeated methylphenidate treatment on methylphenidate self-administration and reinstatement in the most validated animal model of ADHD, the spontaneously hypertensive rat (SHR), and Wistar rat, strain representing the "normal" heterogeneous population.Rats were administered intraperitoneally with saline or methylphenidate (2 mg/kg) for 14 days, prior to experiments. Thereafter, responses for intravenous methylphenidate under the fixed ratio (FR1 and FR3) and progressive ratio (PR) schedules were assessed. Extinction experiments followed, as well as tests to determine the ability of intraperitoneal administration of methylphenidate (2 and 5 mg/kg) to reinstate extinguished drug-seeking behaviors in rats.Previous exposure to methylphenidate enhanced methylphenidate self-administration in Wistar rats but not in SHR (FR3). Methylphenidate pretreatment reduced responding for methylphenidate in SHR but did not affect self-administration behaviors of Wistar rats (PR). Methylphenidate pre-exposure robustly reinstated drug-seeking behaviors in Wistar rats, but not in SHR.The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients.