Algahim Mohame Fodhl, Yang Pamela Boi, Burau Keith Dean, Swann Allan Craig, Dafny Nachum
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas 77225, USA.
Cent Nerv Syst Agents Med Chem. 2010 Sep 1;10(3):247-57. doi: 10.2174/1871524911006030247.
Attention Deficit Hyperactivity Disorder (ADHD) is a common behavioral disorder of children and is treated by psychostimulants. Psychostimulant exposure to children at the time of neuronal development can cause behavioral and physiological changes continuing during adulthood. Most of the studies on psychostimulants investigate the acute effects of the drug. The objective of this study was to investigate whether acute or chronic exposure to methylphenidate (MPD), the drug most often used to treat ADHD in children, will modulate the diurnal activity pattern of young rats. Maintaining the diurnal activity pattern is a physiological process that regulates the internal homeostasis. Dose response protocol was used to study the effect of acute and chronic MPD in four young post natal day 40 (P 40) rat groups, (each N=8), as follows: saline (control) group, and 0.6, 2.5, or 10.0 mg/kg i.p. MPD groups, respectively. The experiment was performed over 11 consecutive days of continuous locomotor activity recording using the open field assay. The data evaluation was divided into four phases as follows: acute, induction, washout and expression phases. There was a dose-dependent increase in the average locomotor activity in the first few hours post-injection. Analysis of the diurnal rhythmic pattern of locomotion in the three dose groups compared to control demonstrated that only the 10.0 mg/kg MPD elicited significant changes in diurnal pattern activity in the washout and the expression phase. In addition, this study indicated that chronic MPD treatment elicits dose dependent anticipation and/or withdrawal and behavioral sensitization.
注意缺陷多动障碍(ADHD)是一种常见的儿童行为障碍,通常使用精神兴奋剂进行治疗。在神经元发育时期接触精神兴奋剂会导致儿童出现行为和生理变化,并持续至成年期。大多数关于精神兴奋剂的研究都集中在药物的急性效应上。本研究的目的是探究急性或慢性接触哌甲酯(MPD,儿童治疗ADHD最常用的药物)是否会调节幼鼠的昼夜活动模式。维持昼夜活动模式是一个调节体内稳态的生理过程。采用剂量反应方案,对四组出生后第40天(P40)的幼鼠(每组N = 8)进行急性和慢性MPD效应研究,分组如下:生理盐水(对照)组,以及腹腔注射0.6、2.5或10.0mg/kg MPD组。使用旷场试验连续记录11天的运动活动,以此进行实验。数据评估分为四个阶段:急性、诱导、洗脱和表达阶段。注射后最初几个小时内,平均运动活动呈剂量依赖性增加。与对照组相比,对三个剂量组运动的昼夜节律模式分析表明,只有10.0mg/kg MPD在洗脱期和表达期引起昼夜模式活动的显著变化。此外,本研究表明,慢性MPD治疗会引起剂量依赖性的预期和/或戒断反应以及行为敏感化。