Zoldi Anna, Kormoczi László, Plesz Szonja B, Adlan Leatitia G, Kekesi Gabriella, Liszli Péter, Nyúl Laszló G, Braunitzer Gábor, Horvath Gyöngyi
Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Department of Image Processing and Computer Graphics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Front Psychiatry. 2025 Sep 1;16:1601714. doi: 10.3389/fpsyt.2025.1601714. eCollection 2025.
Automated homecage systems provide valuable insights into rodent behavior in an undisturbed environment over extended periods. This study aims to identify behavioral differences between Long Evans (LE) rats (control) and a novel triple-hit schizophrenia model (Lisket), developed through selective breeding based on schizophrenia-related behavioral alterations following juvenile social isolation and ketamine treatment.
Pain sensitivity (tail-flick test), behavioral activity, and cognitive function were assessed in acute tests (Ambitus test) and chronic conditions (HomeManner system with a delay discount paradigm).
Lisket rats exhibited significantly increased pain sensitivity, reduced locomotion and exploration, and impaired learning ability. While all LE rats learned to prefer the large-dose reward tray, only 69% of Lisket rats demonstrated this preference. Although Lisket rats displayed significant cognitive deficits, particularly under delay conditions, no clear signs of heightened impulsivity were detected. Personalized analysis revealed substantial interindividual variability in both groups, accompanied by high intraindividual fluctuations across different parameters.
This study provides the first comprehensive behavioral characterization of the Lisket model, a triple-hit schizophrenia-like rat strain derived from Long Evans rats, under both acute and chronic testing conditions. The automated, experimenter-free approach used in this study offers a promising tool for complex behavioral assessment. Furthermore, the findings emphasize the importance of individualized behavioral analysis alongside group-level assessments to enhance the translational validity of preclinical neuropsychiatric research.
自动化笼养系统能在较长时间内，在不受干扰的环境中为啮齿动物行为提供有价值的见解。本研究旨在确定长 Evans（LE）大鼠（对照组）与一种新型三打击精神分裂症模型（Lisket）之间的行为差异，该模型是通过基于幼年社会隔离和氯胺酮治疗后与精神分裂症相关的行为改变进行选择性育种而开发的。
在急性试验（Ambitus 试验）和慢性条件（具有延迟折扣范式的 HomeManner 系统）下评估疼痛敏感性（甩尾试验）、行为活动和认知功能。
Lisket 大鼠表现出疼痛敏感性显著增加、运动和探索减少以及学习能力受损。虽然所有 LE 大鼠都学会了更喜欢大剂量奖励托盘，但只有 69%的 Lisket 大鼠表现出这种偏好。尽管 Lisket 大鼠表现出明显的认知缺陷，尤其是在延迟条件下，但未检测到明显的冲动性增强迹象。个性化分析显示两组个体间存在显著差异，同时不同参数的个体内波动也很大。
本研究首次在急性和慢性测试条件下，对源自长 Evans 大鼠的三打击精神分裂症样大鼠品系 Lisket 模型进行了全面的行为特征描述。本研究中使用的自动化、无需实验者的方法为复杂行为评估提供了一个有前景的工具。此外，研究结果强调了在进行组水平评估的同时进行个性化行为分析对于提高临床前神经精神研究转化效度的重要性。
