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Hyperactivity and impaired attention in Gamma aminobutyric acid transporter subtype 1 gene knockout mice

  • Long Chen (a1), Xiaobo Yang (a1), Xiaoyong Zhou (a1), Cuicui Wang (a1), Xue Gong (a1), Biqin Chen (a2) and Yinghui Chen (a1)...
Abstract
Objectives

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder. It is conceivable that Gamma aminobutyric acid (GABA) neurotransmission is implicated in the pathophysiology of ADHD. This study investigated the effect of GABA transporter 1 (GAT-1) on the anxiety-like behaviours and cognitive function in knockout mice.

Methods

In all, 20 adult male mice were divided into two groups: wild-type (WT) group and GAT-1−/− group. The open field test, elevated O-maze (EZM) and Morris water maze were used to evaluate behavioural traits relevant to ADHD.

Results

Compared with WT mice, the GAT-1−/− mice travelled longer and displayed an enhanced kinematic velocity with the significant reduction of rest time in the open field test (p<0.05). The EZM showed that GAT-1−/− mice displayed a significant increase in total entries into the open sectors and the closed sectors compared with the WT mice. The WT mice showed shorter latencies after the training session (p<0.01), whereas the GAT-1−/− mice made no difference during probe test, the GAT-1−/− mice spent less time in the target quadrant (p<0.01).

Conclusion

Our results demonstrated that GAT-1−/− mice have phenotypes of hyperactivity, impaired sustained attention and learning deficiency, and the performance of GAT-1−/− mice is similar to ADHD symptoms. So, the study of the GAT-1−/− mice may provide new insights into the mechanisms and the discovery of novel therapeutics for the treatment of ADHD.

Copyright
Corresponding author
Yinghui Chen, Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China. Tel: +86 21 3418 9990; Fax: +86 21 5703 9502; E-mail: yinghuichen@fudan.edu.cn
Biqin Chen, Department of Pediatric, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China. Tel: +86 21 3418 9990; Fax: +86 21 5703 9502; E-mail: binqinc@163.com
Footnotes
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These three authors contributed equally to this work.

Footnotes
References
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Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
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