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Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene

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ADHD Attention Deficit and Hyperactivity Disorders

Abstract

GABAergic interneuron loss, maturational delay or imbalance of glutamatergic to GABAergic signaling has been implicated in several neuropsychiatric disorders including Tourette syndrome and attention-deficit/hyperactivity disorder (ADHD). In schizophrenia, decreases in parvalbumin (PV), somatostatin (Sst) and glutamic acid decarboxylase (GAD) RNA have been observed and seem to indicate a failure in maturation in PV and Sst neurons. In Tourette syndrome, which has a high level of comorbid ADHD, reduced numbers of parvalbumin expressing neurons have been observed in the basal ganglia of affected patients. In addition, polymorphisms in the GAD1 gene that codes for GAD67 protein have been associated with ADHD. We have examined whether mice with a disrupted Gad67 allele, the Gad67 GFP knock-in mice (Gad67-GFP+/−), display abnormal locomotor behavior or altered anxiety behavior on the elevated plus maze. We found that Gad67-GFP+/− mice displayed a mild hyperactivity compared to control littermates.

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Acknowledgements

The author wishes to thank Dr. Flora Vaccarino for support and editorial review, Dr. Yanagawa for sharing the Gad67-GFP+/ mouse line and Dr. Russ Barkley for helpful discussion. Support was provided by National Institutes of Health, NIH: K01MH087845 and Brain and Behavior Research Foundation NARSAD Young Investigator Award. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Correspondence to Karen Müller Smith.

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The author declares that she has no conflict of interest.

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This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Yale University Institutional Animal Care and Use Committee (Protocol Number 2012-07621).

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Smith, K.M. Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene. ADHD Atten Def Hyp Disord 10, 267–271 (2018). https://doi.org/10.1007/s12402-018-0254-0

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