Guerriero Réjean M, Hayes Margaret M, Dhaliwal Sharon K, Ren Jia-Qian, Kosofsky Barry E
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital-East, Charlestown, USA.
Biol Psychiatry. 2006 Dec 1;60(11):1171-80. doi: 10.1016/j.biopsych.2006.03.034. Epub 2006 Jun 14.
Methylphenidate (MPH), the most commonly prescribed medication for childhood attention-deficit/hyperactivity disorder (ADHD), shares chemical and mechanistic similarities to cocaine which has stimulated research to address the addiction liability following treatment.
Utilizing locomotor sensitization we examined the consequences of recurrent MPH versus cocaine treatment during preadolescence in altering cocaine-induced locomotor behavior in adolescent and adult mice. Black Swiss Webster mice were treated with MPH, cocaine, or saline during preadolescence. To test whether MPH pretreatment during preadolescence contributed to an altered sensitivity to cocaine during adolescence, these mice were treated with recurrent cocaine or saline during adolescence. All mice were challenged with cocaine as adults.
Recurrent MPH treatment, unlike cocaine treatment in preadolescent mice, had no effect on locomotor sensitization to cocaine during adolescence or adulthood, as compared with saline controls. Furthermore, unlike cocaine, administration of MPH in adolescence did not augment the response to cocaine challenge.
MPH treatment during preadolescence does not increase subsequent sensitivity to cocaine, whereas cocaine treatment does. Thus, MPH treatment during preadolescence does not appear to persistently induce long-term adaptations, which may underlie an enhanced liability for subsequent drug abuse.
哌甲酯(MPH)是治疗儿童注意力缺陷多动障碍(ADHD)最常用的药物,它与可卡因在化学和作用机制上有相似之处,这激发了关于治疗后成瘾倾向的研究。
利用运动敏化,我们研究了青春期前反复给予MPH与可卡因治疗对青春期和成年小鼠可卡因诱导的运动行为的影响。在青春期前,对瑞士黑种Webster小鼠给予MPH、可卡因或生理盐水治疗。为了测试青春期前MPH预处理是否会导致青春期对可卡因的敏感性改变,这些小鼠在青春期接受反复的可卡因或生理盐水治疗。所有小鼠成年后均用可卡因进行激发试验。
与生理盐水对照组相比,青春期前反复给予MPH治疗,与青春期前给予可卡因治疗不同,对青春期或成年期可卡因诱导的运动敏化没有影响。此外,与可卡因不同,青春期给予MPH不会增强对可卡因激发试验的反应。
青春期前给予MPH治疗不会增加随后对可卡因的敏感性,而给予可卡因治疗则会增加。因此,青春期前给予MPH治疗似乎不会持续诱导长期适应性变化,而这种变化可能是随后药物滥用易感性增加的基础。