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Effects of the GABA-uptake inhibitor tiagabine in rat globus pallidus

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Abstract

To elucidate the cellular action of tiagabine, an inhibitor of GAT-1 GABA transporter, in the globus pallidus, whole-cell patch-clamp recordings were made from rat globus pallidus neurons in the acutely prepared brain slice. Superfusion of tiagabine significantly prolonged the decay kinetics of both action potential-dependent and -independent (tetrodotoxin-resistant) inhibitory postsynaptic currents (IPSCs) that were mediated by GABAA receptors. Furthermore, it decreased the frequency of these IPSCs. The latter effect was reversed by the GABAB receptor antagonist CGP55845, which alone had no effect, suggesting the involvement of presynaptic GABAB receptors. Thus, tiagabine could inhibit or disinhibit globus pallidus neurons by increasing the activation of the GABAA receptors and presynaptic GABAB receptors, respectively. In the behaving animal, tiagabine when injected unilaterally into the globus pallidus caused consistent ipsilateral rotation of the rats indicative of increased inhibition of globus pallidus activity. This finding could be explained by the proposition that in the presence of tiagabine, prolonged action of GABA on GABA receptors would dominate over the inhibitory effect of tiagabine on GABA release. Our findings on the electrophysiological and behavioral effects of tiagabine in globus pallidus suggest that this basal ganglia nucleus is one of the sites of action of tiagabine and provides a rationale for investigating its involvement in epilepsy.

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Acknowledgements

This work was supported by a grant awarded to W.H. Yung by the Research Grants Council of Hong Kong (CUHK 4080/00M).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    Lei Chen & Wing-Ho Yung

  2. Department of Physiology, Medical College of Qingdao University, Qingdao, China

    Lei Chen

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  1. Lei Chen
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  2. Wing-Ho Yung
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Correspondence to Wing-Ho Yung.

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Chen, L., Yung, WH. Effects of the GABA-uptake inhibitor tiagabine in rat globus pallidus. Exp Brain Res 152, 263–269 (2003). https://doi.org/10.1007/s00221-003-1549-7

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  • DOI: https://doi.org/10.1007/s00221-003-1549-7

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