id_908. THE EFFECT OF SSR504734, A GLYCINE TRANSPORTER TYPE 1 INHIBITOR, ON ANXIETY RELATED BEHAVIOR IN A MOUSE MODEL OF TEMPORAL LOBE EPILEPSY
Weronika Woźniak1,2, Nikola Gapińska1,2, Piotr Wlaź1, Krzysztof Kamiński3, Marcin Jakubiec3, Michał Abram3, Katarzyna Ciepiela4, 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 Selvita S.A., Bobrzyńskiego 14, 30-348 Kraków, Poland
INTRODUCTION: Background: Epilepsy affects approximately 1% of the global population and, despite significant advances in research, remains a major therapeutic challenge. In addition to recurrent seizures, patients with epilepsy frequently experience a substantial burden of comorbidities, particularly psychiatric disorders, including anxiety. Preclinical studies suggest that selective inhibition of the glycine transporter GlyT1 may influence susceptibility to epileptic seizures.
AIM(S): The aim of the present study was to evaluate the effect of the GlyT1 inhibitor SSR504734 on anxiety-related behavior in mice subjected to amygdala kindling, an experimental model of temporal lobe epilepsy.
METHOD(S): Methods: The experiments were conducted on male CD-1 mice divided into four groups: kindled and sham (non-kindled) animals. Mice received SSR504734 at a dose of 30 mg/kg or physiological saline daily throughout the stimulation period. Seizure severity was assessed using the Racine scale, and animals were considered kindled after five consecutive generalized seizures. Anxiety-related behaviors were evaluated by using the elevated plus maze and the light/dark box tests. In addition, general locomotor activity was measured to assess the effect of treatments on motor performance.
RESULTS: Results: No effects were observed on spontaneous activity and anxiety behaviour in the light dark box test. However, mice treated with SSR504734 spent significantly more time in the open arms in the elevated plus maze test. In addition, amygdala stimulation was associated with behavioral changes compared with sham groups.
CONCLUSIONS: Conclusion: The elevated plus maze results indicate that SSR504734 may reduce anxiety-like behavior, suggesting a potential anxiolytic effect of this compound.
FINANCIAL SUPPORT: Research project financed by the National Science Center UMO 2021/41/B/NZ7/00328.