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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
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
Corresponding

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.

Type
Original Articles
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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Footnotes

These three authors contributed equally to this work.

References

1. Faraone, SV, Sergeant, J, Gillberg, C, Biederman, J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2003;2:104113.Google Scholar
2. Faraone, SV. Genetics of adult attention-deficit/hyperactivity disorder. Psychiatr Clin North Am 2004;27:303321.CrossRefGoogle ScholarPubMed
3. Faraone, SV, Perlis, RH, Doyle, AE et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005;57:13131323.CrossRefGoogle ScholarPubMed
4. Wu, J, Xiao, H, Sun, H, Zou, L, Zhu, LQ. Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol 2012;45:605620.CrossRefGoogle ScholarPubMed
5. Lesch, KP, Waider, J. Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. Neuron 2012;76:175191.CrossRefGoogle ScholarPubMed
6. Thapar, A, O’Donovan, M, Owen, MJ. The genetics of attention deficit hyperactivity disorder. Hum Mol Genet 2005;14(2):R275R282.CrossRefGoogle ScholarPubMed
7. Bidwell, LC, McClernon, FJ, Kollins, SH. Cognitive enhancers for the treatment of ADHD. Pharmacol Biochem Behav 2011;99:262274.CrossRefGoogle ScholarPubMed
8. Stein, MA, Waldman, ID, Sarampote, CS et al. Dopamine transporter genotype and methylphenidate dose response in children with ADHD. Neuropsychopharmacology 2005;30:13741382.Google ScholarPubMed
9. Reichling, DB, Basbaum, AI. Contribution of brainstem GABAergic circuitry to descending antinociceptive controls: II. Electron microscopic immunocytochemical evidence of GABAergic control over the projection from the periaqueductal gray to the nucleus raphe magnus in the rat. J Comp Neurol 1990;302:378393.CrossRefGoogle ScholarPubMed
10. Krajnc, D, Neff, NH, Hadjiconstantinou, M. Glutamate, glutamine and glutamine synthetase in the neonatal rat brain following hypoxia. Brain Res 1996;707:134137.CrossRefGoogle ScholarPubMed
11. Garbutt, JC, van Kammen, DP. The interaction between GABA and dopamine: implications for schizophrenia. Schizophr Bull 1983;9:336353.CrossRefGoogle Scholar
12. Santiago, M, Machado, A, Cano, J. Regulation of the prefrontal cortical dopamine release by GABAA and GABAB receptor agonists and antagonists. Brain Res 1993;630:2831.CrossRefGoogle Scholar
13. van der Kooij, MA, Glennon, JC. Animal models concerning the role of dopamine in attention-deficit hyperactivity disorder. Neurosci Biobehav Rev 2007;31:597618.CrossRefGoogle ScholarPubMed
14. Ueda, Y, Willmore, LJ. Hippocampal gamma-aminobutyric acid transporter alterations following focal epileptogenesis induced in rat amygdala. Brain Res Bull 2000;52:357361.CrossRefGoogle ScholarPubMed
15. Guastella, J, Nelson, N, Nelson, H et al. Cloning and expression of a rat brain GABA transporter. Science 1990;249:13031306.CrossRefGoogle ScholarPubMed
16. Chiu, CS, Jensen, K, Sokolova, I et al. Number, density, and surface/cytoplasmic distribution of GABA transporters at presynaptic structures of knock-in mice carrying GABA transporter subtype 1-green fluorescent protein fusions. J Neurosci 2002;22:1025110266.Google ScholarPubMed
17. Jensen, K, Chiu, CS, Sokolova, I, Lester, HA, Mody, I. GABA transporter-1 (GAT1)-deficient mice: differential tonic activation of GABAA versus GABAB receptors in the hippocampus. J Neurophysiol 2003;90:26902701.CrossRefGoogle ScholarPubMed
18. Yang, P, Cai, G, Cai, Y, Fei, J, Liu, G. Gamma aminobutyric acid transporter subtype 1 gene knockout mice: a new model for attention deficit/hyperactivity disorder. Acta Biochim Biophys Sin (Shanghai) 2013;45:578585.CrossRefGoogle Scholar
19. Fuss, J, Ben, AN, Vogt, MA et al.. Voluntary exercise induces anxiety-like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis. Hippocampus 2010;20:364376.Google ScholarPubMed
20. Tang, YP, Shimizu, E, Dube, GR et al. Genetic enhancement of learning and memory in mice. Nature 1999;401:6369.Google Scholar
21. Morris, RG, Garrud, P, Rawlins, JN, O’Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 1982;297:681683.CrossRefGoogle ScholarPubMed
22. Gong, N, Li, Y, Cai, GQ et al. GABA transporter-1 activity modulates hippocampal theta oscillation and theta burst stimulation-induced long-term potentiation. J Neurosci 2009;29:1583615845.CrossRefGoogle ScholarPubMed
23. Huang, Y, Hu, Z, Liu, G, Zhou, W, Zhang, Y. Cytokines induced by long-term potentiation (LTP) recording: a potential explanation for the lack of correspondence between learning/memory performance and LTP. Neuroscience 2013;231:432443.CrossRefGoogle ScholarPubMed
24. Yin, P, Cao, AH, Yu, L, Guo, LJ, Sun, RP, Lei, GF. ABT-724 alleviated hyperactivity and spatial learning impairment in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder. Neurosci Lett 2014;580:142146.CrossRefGoogle ScholarPubMed
25. Guo, T, Yang, C, Guo, L, Liu, K. A comparative study of the effects of ABT-418 and methylphenidate on spatial memory in an animal model of ADHD. Neurosci Lett 2012;528:1115.CrossRefGoogle Scholar
26. Liu, LL, Yang, J, Lei, GF, Wang, GJ, Wang, YW, Sun, RP. Atomoxetine increases histamine release and improves learning deficits in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat. Basic Clin Pharmacol Toxicol 2008;102:527532.CrossRefGoogle Scholar
27. Steiniger, B, Kretschmer, BD. Glutamate and GABA modulate dopamine in the pedunculopontine tegmental nucleus. Exp Brain Res 2003;149:422430.CrossRefGoogle ScholarPubMed
28. Liu, GX, Cai, GQ, Cai, YQ et al. Reduced anxiety and depression-like behaviors in mice lacking GABA transporter subtype 1. Neuropsychopharmacology 2007;32:15311539.CrossRefGoogle Scholar
29. Willcutt, EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 2012;9:490499.CrossRefGoogle ScholarPubMed
30. Shi, J, Cai, Y, Liu, G et al. Enhanced learning and memory in GAT1 heterozygous mice. Acta Biochim Biophys Sin (Shanghai) 2012;44:359366.CrossRefGoogle Scholar
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