Methylphenidate disrupts social play behavior in adolescent rats.
Methylphenidate disrupts social play behavior in adolescent rats.
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哌醋甲酯会扰乱青春期大鼠的社交游戏行为。
DOI：
10.1038/npp.2008.10
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Schoffelmeer,AntonNM
中科院分区：
文献类型：
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作者：
Vanderschuren,LoukJMJ;Trezza,Viviana;Griffioen-Roose,Sanne;Schiepers,OlgaJG;VanLeeuwen,Natascha;DeVries,TacoJ;Schoffelmeer,AntonNM
哌醋甲酯是治疗注意力缺陷多动障碍（ADHD）的首选药物，但其作用机制尚不完全清楚。哌醋甲酯的认知效应已被广泛研究，但对其对自发社会行为的影响知之甚少。在青春期，大鼠表现出一种特征性的、高度活跃的社会行为形式，称为社会游戏行为，这对社会和认知发展至关重要。我们研究了哌醋甲酯影响大鼠社会游戏行为的神经行为机制。哌醋甲酯（0.3-3.0 mg/kg，sc或po）可抑制社交游戏行为，但不改变一般社交兴趣。哌醋甲酯的这种作用不依赖于社交游戏的基线水平，也不继发于运动的变化。此外，哌醋甲酯的玩耍抑制作用不受耐受性或致敏性的影响。哌醋甲酯阻断了对游戏的启动和对游戏启动的反应。去甲肾上腺素再摄取抑制剂托莫西汀（也用于治疗ADHD）模拟哌甲酯的作用，并被α-2肾上腺素受体拮抗剂阻断。此外，亚有效剂量的哌甲酯和托莫西汀联合给药抑制了社交游戏。然而，阻断α-1肾上腺素受体、β肾上腺素受体或多巴胺受体并不改变哌醋甲酯的作用。这些数据表明，哌醋甲酯选择性地阻止青春期大鼠通过去甲肾上腺素能机制的行为剧目的最有力的一部分。我们认为哌醋甲酯对社交游戏的影响反映了其在ADHD中的治疗效果，即改善行为抑制。然而，考虑到社交游戏对发育的重要性，这些发现也可能表明哌醋甲酯的不良副作用。
Methylphenidate is the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), but its mechanism of action is incompletely understood. The cognitive effects of methylphenidate have been extensively studied, but little is known about its effects on spontaneous social behavior. During adolescence, rats display a characteristic, highly vigorous form of social behavior, termed social play behavior, which is of critical importance for social and cognitive development. We investigated the neurobehavioral mechanisms by which methylphenidate affects social play behavior in rats. Methylphenidate (0.3–3.0 mg/kg, sc or po) abolished social play behavior, without altering general social interest. This effect of methylphenidate did not depend upon the baseline level of social play and was not secondary to changes in locomotion. Furthermore, the play-suppressant effect of methylphenidate was not subject to tolerance or sensitization. Methylphenidate blocked both the initiation to play and the responsivity to play initiation. The effect of methylphenidate was mimicked by the noradrenaline reuptake inhibitor atomoxetine, which is also used for the treatment of ADHD, and was blocked by an α-2 adrenoceptor antagonist. In addition, combined administration of subeffective doses of methylphenidate and atomoxetine suppressed social play. However, blockade of α-1 adrenoceptors, β-adrenoceptors, or dopamine receptors did not alter the effect of methylphenidate. These data show that methylphenidate selectively blocks the most vigorous part of the behavioral repertoire of adolescent rats through a noradrenergic mechanism. We suggest that the effect of methylphenidate on social play is a reflection of its therapeutic effect in ADHD, that is, improved behavioral inhibition. However, given the importance of social play for development, these findings may also indicate an adverse side effect of methylphenidate.