Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University Munich, Munich, Germany.
Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
Epilepsy Behav. 2021 Feb;115:107689. doi: 10.1016/j.yebeh.2020.107689. Epub 2021 Jan 5.
Ethical decisions about an allowance for animal experiments need to be based on scientifically sound information about the burden and distress associated with the experimental procedure and models. Thereby, species differences need to be considered for recommendations regarding evidence-based severity assessment and refinement measures.
A comprehensive analysis of behavioral patterns and corticosterone or its metabolites in serum and feces was completed in kindled mice. The impact of kindling via two different stimulation sites in the amygdala and hippocampus was determined. Data were compared to those from naive and electrode-implanted groups.
Amygdala and hippocampus kindled mice exhibited comparable behavioral patterns with increased activity in the open field, reduced anxiety-associated behavior in the elevated-plus maze, and increased anhedonia-associated behavior in the saccharin preference test. In addition, repeated stimulation of the hippocampus caused a reduction in burrowing behavior and an increase in active social interaction. Levels of corticosterone and its metabolites were not altered in serum or feces, respectively. A comparison of mouse data with findings from amygdala kindled rats confirmed pronounced species differences in behavioral patterns associated with the kindling process.
Taken together the findings suggest a severity classification for the mouse kindling paradigms as moderate regardless of the stimulation site. The outcome of the species comparison provides valuable guidance for species selection for studies exploring behavioral comorbidities. In this context, it is emphasized that the mouse kindling paradigms seem to be well suited for studies exploring the link between ictal events and network alterations on the one hand, and hyperactivity and anhedonia-associated behavior on the other hand. Moreover, the underlying pathophysiological mechanisms and the impact of therapeutic interventions on these behavioral alterations can be studied in these paradigms providing guidance for the clinical management of respective psychiatric comorbidities in patients.
动物实验津贴的伦理决策需要基于与实验程序和模型相关的负担和痛苦的科学依据。因此，需要考虑物种差异，为基于证据的严重程度评估和改进措施提供建议。
在点燃的小鼠中完成了对行为模式和皮质酮或其代谢物在血清和粪便中的全面分析。确定了在杏仁核和海马体的两个不同刺激部位进行点燃的影响。将数据与来自未点燃和电极植入组的数据进行了比较。
杏仁核和海马体点燃的小鼠表现出相似的行为模式，表现为旷场活动增加，高架十字迷宫中焦虑相关行为减少，蔗糖偏好测试中快感缺失相关行为增加。此外，海马体的重复刺激导致挖掘行为减少和主动社交互动增加。皮质酮及其代谢物的水平在血清或粪便中均未改变。将小鼠数据与杏仁核点燃大鼠的发现进行比较，证实了与点燃过程相关的行为模式存在明显的物种差异。
总的来说，这些发现表明，无论刺激部位如何，小鼠点燃模型的严重程度分类为中度。物种比较的结果为探索行为共病的研究提供了有价值的物种选择指导。在这种情况下，强调小鼠点燃模型似乎非常适合研究癫痫发作事件与网络改变之间的联系，以及另一方面与过度活跃和快感缺失相关的行为之间的联系。此外，这些模型可以研究潜在的病理生理机制以及治疗干预对这些行为改变的影响，为患者相应的精神共病的临床管理提供指导。
