The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice.
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 (1mg/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.
Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: salat.kinga@gmail.com.
Kinga
K
Sałat
Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Adrian
A
Podkowa
Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Szczepan
S
Mogilski
Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Kraków, Poland.
Paula
P
Zaręba
Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Kraków, Poland.
Katarzyna
K
Kulig
Faculty of Production Engineering, Warsaw University of Life Sciences, Warszawa, Poland.
Robert
R
Sałat
Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Natalia
N
Malikowska
Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland.
Barbara
B
Filipek
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D058805:GABA Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D009557:Nipecotic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D012601:Scopolamine; D000078308:Tiagabine
D058805:GABA Uptake Inhibitors; D009557:Nipecotic Acids; D012601:Scopolamine; D000078308:Tiagabine
Fear-motivated memory; GABA transporter 1 (GAT1); Scopolamine-induced memory deficits; Spatial memory; Tiagabine