Kalinowski Leanna, Connor Carly, Somanesan Rathini, Carias Emily, Richer Kaleigh, Smith Lauren, Martin Connor, Mackintosh Macauley, Popoola Daniel, Hadjiargyrou Michael, Komatsu David E, Thanos Panayotis K
Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA.
Department of Psychology, University at Buffalo, Buffalo, NY, USA.
Dev Psychobiol. 2020 Mar;62(2):170-180. doi: 10.1002/dev.21902. Epub 2019 Aug 27.
Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self-administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low-dose (LD), or high-dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1-week abstinence; after three repeats of this cycle, there was a 5-week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety- and depressive-like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive- and anxiety-like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.
哌甲酯（MP）是一种常用于治疗注意力缺陷多动障碍患者的精神振奋药物，且常被健康个体非法使用，服药间隙与学校放假时间相吻合。本研究考察了间歇性禁药期如何影响大鼠长期口服MP自我给药后的生理和行为效应，以及在长期停药后这些效应是否持续存在。从出生后第28天开始，大鼠分别口服水、低剂量（LD）或高剂量（HD）的MP。这种每日给药持续三周，随后停药一周；在重复这个周期三次后，有一个为期5周的停药期。在整个研究过程中，我们检测了体重、食物摄入量、运动活动以及焦虑和抑郁样行为。在治疗阶段，HD MP降低了体重、食物摄入量以及抑郁和焦虑样行为，同时增加了运动活动。在间歇性禁药期间，MP对运动活动的影响消失。在长期停药期间，HD MP的大多数效应都恢复到了对照水平，但体重减轻和抗焦虑效应除外。这些发现表明，间歇性接触慢性MP会导致生理和行为效应，而这些效应在长期停药后大多是可逆的。
