Carias Emily, Fricke Dennis, Vijayashanthar Abisha, Smith Lauren, Somanesan Rathini, Martin Connor, Kalinowski Leanna, Popoola Daniel, Hadjiargyrou Michael, Komatsu David E, Thanos Panayotis K
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY, USA.
New York Institute of Technology, Department of Life Sciences, Old Westbury, NY, USA.
Behav Brain Res. 2019 Jan 1;356:189-196. doi: 10.1016/j.bbr.2018.08.014. Epub 2018 Aug 24.
Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 h, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 h, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley's three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend's off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks).
哌甲酯（MP）是治疗注意力缺陷多动障碍（ADHD）时常用的精神兴奋药物。我们最近报道了健康大鼠长期使用MP的行为和发育影响。本研究调查了周末禁欲中断长期MP治疗如何改变长期MP治疗的行为和生理后果，以及长期禁欲是否会逆转观察到的影响。将雄性斯普拉格-道利大鼠分为三个治疗组之一：水（W）；低剂量（LD）MP；高剂量（HD）MP。持续13周，大鼠每周工作日有1小时可从装有4 mg/kg MP（LD）、30 mg/kg MP（HD）或水（W）的瓶子中饮水，接下来7小时可从装有10 mg/kg MP（LD）、60 mg/kg MP（HD）或水（W）的瓶子中饮水。在周末以及紧接着治疗阶段的为期5周的禁欲阶段，所有动物仅饮用清水。在整个治疗阶段，无论周末是否禁欲，长期使用MP均导致食物和液体摄入量以及体重显著下降。此外，高剂量MP暴露产生了以下行为影响：旷场和昼夜运动活动增加；强迫游泳试验中不动潜伏期增加，不动时间减少；旷场试验中中央活动增加，高架十字迷宫开放臂停留时间百分比增加；在克劳利三室社交试验中社交联系和记忆力增加。在延长的（5周）禁欲阶段，所有这些影响均被逆转，而高剂量MP处理的大鼠液体摄入量增加。这些结果表明，间歇性短暂禁欲期（周末不治疗）产生的行为和发育影响与先前报道的长期（每周7天）MP治疗相同，但在延长的禁欲期（5周）后是可逆的。
