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

Published online by Cambridge University Press:  15 June 2015

Long Chen ,
Xiaobo Yang ,
Xiaoyong Zhou ,
Cuicui Wang ,
Xue Gong ,
Biqin Chen  and
Yinghui Chen
Long Chen
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
Xiaobo Yang
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
Xiaoyong Zhou
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
Cuicui Wang
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
Xue Gong
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
Biqin Chen*
Affiliation:
Department of Pediatric, Jinshan Hospital, Fudan University, Shanghai, China
Yinghui Chen*
Affiliation:
Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China
*
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
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
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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.

Keywords

attention-deficit hyperactivity disorderGamma aminobutyric acidGABA transporters 1
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 6 , December 2015 , pp. 368 - 374
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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Footnotes

†

These three authors contributed equally to this work.

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