Department of Psychology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Neuropsychopharmacology. 2012 Oct;37(11):2446-55. doi: 10.1038/npp.2012.103. Epub 2012 Jul 4.
People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.
患有注意力缺陷多动障碍(ADHD)的人经常会出现睡眠问题,而这些问题常常会因他们服用哌醋甲酯来治疗 ADHD 症状而加剧。许多睡眠变化与内在生物钟的变化一致。本研究旨在确定单独使用哌醋甲酯是否会改变生物钟的特性。研究人员在光照-黑暗周期和持续黑暗中检查了年轻雄性小鼠,并对自由活动小鼠的行为活动、睡眠和视交叉上核(SCN)的电活动进行了记录。饮用水中的哌醋甲酯(0.08%)显著增加了午夜到深夜的活动量,并导致活动和睡眠相对于光照-黑暗周期的开始时间延迟。虽然运动水平在治疗结束后恢复到基线水平,但同步的相位角至少需要一周才能恢复到基线水平。在持续黑暗中,哌醋甲酯延长了轮跑和一般运动节律的自由运行周期。当治疗结束时,自由运行周期要么保持稳定,要么仅部分恢复到基线水平。哌醋甲酯还改变了 SCN 中的电活动节律。它诱导节律的低谷延迟、节律幅度增加和节律变异性降低。这些观察结果表明,哌醋甲酯改变了内在的生物钟。观察到的变化与促进入睡性失眠的时钟改变一致。