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

Acta Neuropsychiatr. 2015 Dec;27(6):368-74. doi: 10.1017/neu.2015.37. Epub 2015 Jun 15.


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: GABA transporters 1; Gamma aminobutyric acid; attention-deficit hyperactivity disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Anxiety / metabolism*
  • Anxiety / psychology*
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Attention Deficit Disorder with Hyperactivity / psychology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • GABA Plasma Membrane Transport Proteins / genetics
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phenotype
  • RNA-Binding Proteins
  • gamma-Aminobutyric Acid / metabolism


  • DNA-Binding Proteins
  • GABA Plasma Membrane Transport Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Slc6a1 protein, mouse
  • Wig1 protein, mouse
  • gamma-Aminobutyric Acid