Memory and Learning in WAG/Rij and Sprague Dawley Rats: Investigating the Effect of “Racial Experience,” Especially on Predisposition to Epilepsy

Yıl 2025, Cilt: 5 Sayı: 2, 102 - 109, 19.09.2025

Burcu Çevreli , Öznur Özge Özcan

https://doi.org/10.62425/jlasp.1660043

Öz

This research sought to investigate how genetic variations influence learning, short-term memory, and long-term memory in rats. In particular, it compared WAG/Rij (WR) rats, which are naturally prone to epilepsy, with Sprague-Dawley (SD) rats. A total of 24 male rats, consisting of 12 Sprague-Dawley (SD) and 12 Wistar (WR) rats, were evaluated using an eight-arm radial maze to examine spatial memory and the retention of learning over time. No significant differences were observed in working memory errors (WME) at 48, 72, 96, 120, and 144 hours (p > 0.05), and similar results were found for reference memory errors (RME). However, WR rats made significantly more RME than SD rats at 48 hours (p = 0.0111, 95% CI: -1.606 to -0.2178). SD rats also completed the maze significantly faster at 96 hours (p = 0.0094) and 120 hours (p = 0.0383) than WR rats. Additionally, on the 4th day of the acquisition trial, WR rats made significantly more total errors than SD rats (p = 0.0045). This research offers fresh perspectives on the variations in learning and memory across different rat strains within various behavioral models. Although SD rats gave better results in short-term memory and faster results in the process of completing the task compared to WR rats, further research is recommended in different behavioral patterns.

Anahtar Kelimeler

Racial Experience , Reference Memory , Spatial Learning , Working Memory

WAG/Rij ve Sprague Dawley Sıçanlarında Hafıza ve Öğrenme: “Irksal Deneyimin” Özellikle Epilepsi Yatkınlığının Üzerindeki Etkisinin Araştırılması

Öz

Bu araştırma, genetik varyasyonların sıçanlarda öğrenmeyi, kısa süreli hafızayı ve uzun süreli hafızayı nasıl etkilediğini araştırmayı amaçlamıştır. Özellikle, doğal olarak epilepsiye yatkın olan WAG/Rij (WR) sıçanlarını Sprague-Dawley (SD) sıçanlarıyla karşılaştırmıştır. 12 Sprague-Dawley (SD) ve 12 Wistar (WR) sıçanından oluşan toplam 24 erkek sıçan, uzaysal hafızayı ve zaman içinde öğrenmenin tutulmasını incelemek için sekiz kollu bir radyal labirent kullanılarak değerlendirilmiştir. 48, 72, 96, 120 ve 144. saatlerde çalışma belleği hatalarında (WME) anlamlı bir fark gözlenmemiştir (p > 0,05) ve referans bellek hataları (RME) için benzer sonuçlar bulunmuştur. Bununla birlikte, WR sıçanları 48. saatte SD sıçanlarına göre anlamlı derecede daha fazla RME yapmıştır (p = 0,0111, %95 GA: -1,606 ila -0,2178). SD sıçanları ayrıca labirenti 96 saatte (p = 0,0094) ve 120 saatte (p = 0,0383) WR sıçanlarından önemli ölçüde daha hızlı tamamladı. Ek olarak, edinim denemesinin 4. gününde, WR sıçanları SD sıçanlarından önemli ölçüde daha fazla toplam hata yaptı (p = 0,0045). Bu araştırma, çeşitli davranış modelleri içindeki farklı sıçan türleri arasında öğrenme ve bellekteki farklılıklar hakkında yeni bakış açıları sunmaktadır. SD sıçanları kısa süreli bellekte daha iyi sonuçlar ve görevi tamamlama sürecinde WR sıçanlarına kıyasla daha hızlı sonuçlar vermiş olsa da, farklı davranış kalıplarında daha fazla araştırma yapılması önerilmektedir.

Anahtar Kelimeler

Çalışma Belleği , Irksal Deneyim , Mekansal Öğrenme , Referans Belleği

Kaynakça

• Blankenship, P. A., Normann, M. C., Donaldson, T. N., Baumeister, J., McNeal, N., Grippo, A. J., et al. (2019). Making waves: Comparing Morris water task performance in rats and prairie voles. Behavioral Brain Research, 360, 7-15. https://doi.org/10.1016/j.bbr.2018.11.032
• Bryda, E. C. (2013). The Mighty Mouse: The impact of rodents on advances in biomedical research. Missouri Medicine, 110(3), 207-211.
• Caine, S. B., Plant, S., Furbish, K., Yerton, M., Smaragdi, E., Niclou, B., et al. (2023). Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs. Psychopharmacology (Berl), 240(9), 2005-2012. https://doi.org/10.1007/s00213-023-06444-1.
• De Deurwaerdère, P., Casarrubea, M., Cassar, D., Radic, M., Puginier, E., Chagraoui, A., et al. (2022). Cannabinoid 1/2 receptor activation induces strain-dependent behavioral and neurochemical changes in genetic absence epilepsy rats from Strasbourg and non-epileptic control rats. Frontiers in Cell Neuroscience, 16, 886033. https://doi.org/10.3389/fncel.2022.886033.
• Ellenbroek, B., & Youn, J. (2016). Rodent models in neuroscience research: Is it a rat race? Disease Models & Mechanisms, 9(10), 1079-1087. https://doi.org/10.1242/dmm.026120.
• Gao, S., Bell, E. C., Zhang, Y., & Liang, D. (2021). Racial disparity in drug disposition in the digestive tract. International Journal of Molecular Sciences, 22(3), 1038. https://doi.org/10.3390/ijms22031038.
• Guitar, N. A., & Roberts, W. A. (2015). The interaction between working and reference spatial memories in rats on a radial maze. Behavioral Processes, 112, 100-107. https:// doi.org/10.1016/j.beproc.2014.10.007.
• Gökçek-Saraç, Ç., Karakurt, S., Adalı, O., & Jakubowska-Doğru, E. (2012). Correlation between hippocampal levels of neural, epithelial, and inducible NOS and spatial learning skills in rats. Behavioral Brain Research, 233(2), 493-499. https:// doi.org/10.1016/j.bbr.2012.08.005.
• Gökçek-Saraç, Ç., Wesierska, M., & Jakubowska-Doğru, E. (2015). Comparison of spatial learning in the partially baited radial-arm maze task between commonly used rat strains: Wistar, Sprague-Dawley, Long-Evans, and outcrossed Wistar/Sprague-Dawley. Learning and Behavior, 43(1), 83-94. https://doi.org/10.3758/s13420-014-0163-9.
• Harker, T. K., & Whishaw, I. Q. (2002). Place and matching-to-place spatial learning affected by rat inbreeding (Dark-Agouti, Fischer 344) and albinism (Wistar, Sprague-Dawley) but not domestication (wild rat vs. Long-Evans, Fischer-Norway). Behavioral Brain Research, 134(1), 467-477. https://doi.org/10.1016/s0166-4328(02)00083-9.
• Guo, X., Asthana, P., Zhai, L., Cheng, K. W., Gurung, S., Huang, J., Wu, J., Zhang, Y., Mahato, A. K., Saarma, M., Ustav, M., Kwan, H. Y., Lyu, A., Chan, K. M., Xu, P., Bian, Z. X., Wong, H. L. X. (2024). Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis. Nature Communication, 3;15(1):1034. https://doi.org/10.1038/s41467-024-45452-3.
• Jaramillo, S., & Zador, A. M. (2014). Mice and rats achieve similar levels of performance in an adaptive decision-making task. Frontiers in Systems Neuroscience, 8, 173. https://doi.org/10.3389/fnsys.2014.00173.
• Junttila, S., Valros, A., Mäki, K., Väätäjä, H., Reunanen, E., & Tiira, K. (2022). Breed differences in social cognition, inhibitory control, and spatial problem-solving ability in the domestic dog (Canis familiaris). Scientific Reports, 12(1), 22529. https://doi.org/10.1038/s41598-022-26991-5.
• Lee, J. W., Jung, M. W. (2025). Memory consolidation from a reinforcement learning perspective. Frontiers in Computational Neuroscience, 8;18:1538741. https://doi.org/10.3389/fncom.2024.1538741.
• Kohler, J., Mei, J., Banneke, S., Winter, Y., Endres, M., & Emmrich, J. V. (2022). Assessing spatial learning and memory in mice: Classic radial maze versus a new animal-friendly automated radial maze allowing free access and not requiring food deprivation. Frontiers in Behavioral Neuroscience, 16, 1013624. https://doi.org/10.3389/fnbeh.2022.1013624.
• Manahan-Vaughan, D., & Schwegler, H. (2011). Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats. Frontiers in Behavioral Neuroscience, 7, 5-7. https://doi.org/10.3389/fnbeh.2011.00007.
• Manukyan, P., Romanova, E., Latanov, A., Shlepnev, P., Sharapkova, A., Garabova, N., et al. (2025). Challenges and insights of transferring animal maze studies principles to human spatial learning research. Scientific Reports, 15(1), 2096. https://doi.org/10.1038/s41598-025-86037-4.
• Vorhees, C. V., Williams, M. T. (2024). Tests for learning and memory in rodent regulatory studies. Current Research in Toxicology, 18;6:100151. https://doi.org/10.1016/j.crtox.2024.100151.
• McQuail, J. A., Dunn, A. R., Stern, Y., Barnes, C. A., Kempermann, G., Rapp, P. R., et al. (2021). Cognitive reserve in model systems for mechanistic discovery: The importance of longitudinal studies. Frontiers in Aging Neuroscience, 12, 607685. https://doi.org/10.3389/fnagi.2020.607685.
• Nollen, N. L., Ahluwalia, J. S., Sanderson Cox, L., Okuyemi, K., Lawrence, D., Samuels, L., et al. (2021). Assessment of racial differences in pharmacotherapy efficacy for smoking cessation: Secondary analysis of the EAGLES randomized clinical trial. JAMA Network Open, 4(1), e2032053. https://doi.org/10.1001/jamanetworkopen.2020.32053.
• Peleh, T., Ike, K. G. O., Wams, E. J., Lebois, E. P., & Hengerer, B. (2019). The reverse translation of a quantitative neuropsychiatric framework into preclinical studies: Focus on social interaction and behavior. Neuroscience & Biobehavioral Reviews, 97, 96-111. https://doi.org/10.1016/j.neubiorev.2018.07.018.
• Ramos, J. M. (2000). Influence of the shape of the experimental room on spatial learning in rats. Physiology & Behavior, 70(3), 351-357. https://doi.org/10.1016/s0031-9384(00)00266-3.
• Sitnikova, E. (2024). Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats). Biomedicines, 7;12(1):122. https://doi.org/10.3390/biomedicines12010122.
• Russomanno, G., Sison-Young, R., Livoti, L. A., Coghlan, H., Jenkins, R. E., Kunnen, S. J., et al. (2023). A systems approach reveals species differences in hepatic stress response capacity. Toxicological Sciences, 196(1), 112-125. https://doi.org/10.1093/toxsci/kfad085.
• Sarmiento, L. F., Lopes da Cunha, P., Tabares, S., Tafet, G., & Gouveia, A. J. (2024). Decision-making under stress: A psychological and neurobiological integrative model. Brain, Behavior, and Immunity - Health, 38, 100766. https://doi.org/10.1016/j.bbih.2024.100766.
• Casillas-Espinosa, P. M., Garcia-Olivares, J., Li, R., Li, C., Yu, C., Formella, A. E., O'Brien, T. J. (2024). Huperzine A suppresses absence seizures in the genetic absence epilepsy rat from Strasbourg (GAERS) model of genetic generalized epilepsy with absence seizures. Epilepsia Open, 9(5):1826-1836. https://doi.org/10.1002/epi4.13016.
• Bárdos, B., Török, H. K., Nagy, I. (2024). Comparison of the exploratory behaviour of wild and laboratory mouse species. Behavioural Processes, 217:105031. https://doi.org/10.1016/j.beproc.2024.105031.
• Kovarova, V., Bordes, J., Mitra, S., Narayan, S., Springer, M., Brix, L. M., Deussing, J. M., Schmidt, M. V. (2025). Deep phenotyping reveals CRH and FKBP51-dependent behavioral profiles following chronic social stress exposure in male mice. Neuropsychopharmacology, 50(3):556-567. https://doi.org/10.1038/s41386-024-02008-9.
• Wijnen, K., Genzel, L., & van der Meij, J. (2024). Rodent maze studies: From following simple rules to complex map learning. Brain Structure and Function, 229(4), 823-841. https://doi.org/10.1007/s00429-024-02771-x.