id_837. EFFECT OF SSR504734, A SELECTIVE GLYCINE TRANSPORTER TYPE 1, IN THE AMYGDALA KINDLING MODEL OF TEMPORAL LOBE EPILEPSY IN MICE
Nikola Gapińska1,2, Ewelina Mitura1, Piotr Wlaź1, Krzysztof Kamiński3, Marcin Jakubiec3, Michał Abram3, Bernadeta Szewczyk4, Anna Rafało-Ulińska4, Katarzyna Ciepiela5, Weronika Woźniak1,2, Agata Matuła1,2, Katarzyna Socała1
1 Biomedical Research Laboratory, Faculty of Biology and Biotechnology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
2 Doctoral School of Quantitative and Natural Sciences, Maria Curie-Skłodowska University, Weteranów 18, 20-038 Lublin, Poland
3 Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
4 Department of Neurobiology, Jerzy Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland
5 Selvita S.A., Bobrzyńskiego 14, 30-348 Kraków, Poland
INTRODUCTION: Glycine transporter type 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations by maintaining the balance between excitatory and inhibitory neurotransmission in the central nervous system. Preclinical evidence indicates that selective inhibition of GlyT1 can modulate seizure susceptibility and influence hippocampal network activity, suggesting a potential role of this transporter in epileptogenesis.
AIM(S): Here, we aimed to investigate the effect of SSR504734, a selective GlyT1 inhibitor, on the progression of epileptogenesis in the amygdala kindling model of temporal lobe epilepsy in mice. Potential behavioral alterations were also assessed, including motor coordination and learning and memory.
METHOD(S): CD-1 male mice were divided into four experimental group: kindled and sham (non-kindled) mice receiving SSR504734 at 30 mg/kg or saline daily throughout the amygdala kindling procedure. Mice were considered fully-kindled until five consecutive generalized seizures were elicited according to Racine scale. To evaluate potential behavioral alterations mice were tested in a two of assays, i.e. spatial memory was assessed in the Morris water maze test and motor coordination in the rotarod test.
RESULTS: SSR504734 did not inhibit the progression of epileptogenesis in kindled mice. Also, no significant differences were observed between kindled and sham mice in any of the behavioral tests.
CONCLUSIONS: The obtained results suggest that SSR504734 does not modulate progression of epileptogenesis in the amygdala kindling model. Furthermore, under the conditions tested, kindling did not induce alterations in motor or cognitive behaviors in mice.
FINANCIAL SUPPORT: Research project financed by the National Science Center UMO-2021/41/B/NZ7/00328.