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The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice

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Abstract

Background

GABAergic neurotransmission is involved in long-term potentiation, a neurophysiological basis for learning and memory. On the other hand, GABA-enhancing drugs may impair memory and learning in humans and animals. The present study aims at investigating the effect of GAT1 inhibitor tiagabine on memory and learning.

Methods

Albino Swiss (CD-1) and C57BL/6J mice were used in the passive avoidance (PA), Morris water maze (MWM) and radial arm water maze (RAWM) tasks. Scopolamine (1 mg/kg ip) was applied to induce cognitive deficits.

Results

In the retention trial of PA scopolamine reduced step-through latency as compared to vehicle-treated mice, and pretreatment with tiagabine did not have any influence on this effect. In MWM the results obtained for vehicle-treated mice, scopolamine-treated group and combined scopolamine + tiagabine-treated mice revealed variable learning abilities in these groups. Tiagabine did not impair learning in the acquisition trial. In RAWM on day 1 scopolamine-treated group made nearly two-fold more errors than vehicle-treated mice and mice that received combined scopolamine and tiagabine. Learning abilities in the latter group were similar to those of vehicle-treated mice in the corresponding trial block on day 1, except for the last trial block, during which tiagabine + scopolamine-injected mice made more errors than control mice and the scopolamine-treated group. In all groups a complete reversal of memory deficits was observed in the last trial block of day 2.

Conclusions

The lack of negative influence of tiagabine on cognitive functions in animals with scopolamine-induced memory impairments may be relevant for patients treated with this drug.

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Abbreviations

CNS:

central nervous system

GABA:

γ-aminobutyric acid

GAT:

GABA transporter

MWM:

Morris water maze

PA:

passive avoidance

RAWM:

radial arm water maze

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Author information

Authors and Affiliations

  1. Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland

    Kinga Sałat, Adrian Podkowa, Szczepan Mogilski, Natalia Malikowska & Barbara Filipek

  2. Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Kraków, Poland

    Paula Zaręba & Katarzyna Kulig

  3. Faculty of Production Engineering, Warsaw University of Life Sciences, Warszawa, Poland

    Robert Sałat

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  1. Kinga Sałat
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Correspondence to Kinga Sałat.

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Sałat, K., Podkowa, A., Mogilski, S. et al. The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice. Pharmacol. Rep 67, 1155–1162 (2015). https://doi.org/10.1016/j.pharep.2015.04.018

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  • DOI: https://doi.org/10.1016/j.pharep.2015.04.018

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