School of Life Sciences and Technology, TongJi University, Shanghai 200092, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Jul;45(7):578-85. doi: 10.1093/abbs/gmt043. Epub 2013 May 8.
Attention deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impaired sustained attention, impulsivity, and is usually accompanied by varying degrees of learning difficulties and lack of motor coordination. However, the pathophysiology and etiology of ADHD remain inconclusive so far. Our previous studies have demonstrated that the gamma aminobutyric acid transporter subtype 1 (GAT1) gene knockout (ko) mouse (gat1-/-) is hyperactive and exhibited impaired memory performance in the Morris water maze. In the current study, we found that the gat1-/- mice showed low levels of attentional focusing and increased impulsivity. In addition, the gat1-/- mice displayed ataxia characterized by defects in motor coordination and balance skills. The hyperactivity in the ko mice was reduced by both methylphenidate and amphetamine. Collectively, these results suggest that GAT1 ko mouse is a new animal model for ADHD studying and GAT1 may be a new target to treat ADHD.
注意缺陷多动障碍(ADHD)的特征是多动、注意力持续受损、冲动,通常伴有不同程度的学习困难和运动协调缺乏。然而,ADHD 的病理生理学和病因至今仍未确定。我们之前的研究表明,γ-氨基丁酸转运体亚型 1(GAT1)基因敲除(ko)小鼠(gat1-/-)是多动的,并在 Morris 水迷宫中表现出记忆能力受损。在本研究中,我们发现 gat1-/- 小鼠表现出注意力集中程度低和冲动性增加。此外,gat1-/- 小鼠表现出共济失调,特征是运动协调和平衡技能缺陷。ko 小鼠的多动行为可被哌甲酯和安非他命减轻。总之,这些结果表明,GAT1ko 小鼠是一种研究 ADHD 的新型动物模型,GAT1 可能是治疗 ADHD 的新靶点。