Ryan-Coats Stellan K, Hughes Sara D, Holz Faith M, Kreger Rachelle B, Koulibali Chauncella I, Khan Humza A, Harris Kylie C, Kelly Anna E, Epps S Alisha
Department of Psychology, Whitworth University, Spokane, WA 99251, United States of America.
Physiol Behav. 2022 May 15;249:113778. doi: 10.1016/j.physbeh.2022.113778. Epub 2022 Mar 9.
A bidirectional comorbidity exists between depression and epilepsy such that patients with epilepsy are at higher risk for developing depression, and vice versa. Each of these conditions individually can be complicated by behavioral effects that worsen quality of life, but less is known about these interactions within the comorbidity of depression and epilepsy. The SwLo rat has been selectively bred for depression-relevant behaviors and exhibits enhanced limbic seizure susceptibility. This study sought to characterize the effects of novelty and stress on the SwLo rodent model of this comorbidity. It was hypothesized that SwLo rats would exhibit altered responses to novelty, reflected in hyperactivity-, anxiety-, sensation seeking-, and/or compulsive behaviors, and that this would be exacerbated with stress. Compared to the SwHi rat (their depression- and epilepsy-resistant counterparts), SwLo rats showed increased entries in all areas of the Open Field Test and spent significantly more time in the light compartment of the Light-Dark Box. SwLo rats also had a significantly higher number of rearing behaviors in the inner squares of the Open Field Test, the closed arms of the Elevated Plus Maze, and both areas of the Light-Dark Box. They demonstrated increased Nestlet shredding but showed no difference in a marble burying task or in latency to consume food in a novelty suppressed feeding task. Interestingly, restraint stress showed little effect on these behaviors, despite increasing corticosterone levels. Combined, these results suggest an increase in exploratory sensation seeking and hypervigilant information-gathering behaviors in the SwLo rat that are not dependent on corticosterone levels. This shows the utility of this model for studying behavioral effects of comorbid depression and epilepsy and allows for their use in identifying underlying mechanisms or screening treatment strategies for this complex comorbidity.
抑郁症和癫痫之间存在双向共病关系，即癫痫患者患抑郁症的风险更高，反之亦然。这两种疾病各自都可能因行为影响而变得复杂，进而降低生活质量，但对于抑郁症和癫痫共病中的这些相互作用，人们了解得较少。SwLo大鼠是针对与抑郁症相关的行为进行选择性培育的，并且表现出增强的边缘系统癫痫易感性。本研究旨在描述新奇感和应激对这种共病的SwLo啮齿动物模型的影响。研究假设SwLo大鼠对新奇感的反应会发生改变，表现为多动、焦虑、寻求刺激和/或强迫行为，并且在应激状态下这种情况会加剧。与SwHi大鼠（它们是抗抑郁和抗癫痫的对照品系）相比，SwLo大鼠在旷场试验的所有区域进入次数增加，并且在明暗箱的亮区停留的时间明显更长。SwLo大鼠在旷场试验的内方格、高架十字迷宫的封闭臂以及明暗箱的两个区域的直立行为次数也显著更多。它们表现出更多的碎棉絮行为，但在大理石掩埋任务或新奇抑制摄食任务中的摄食潜伏期方面没有差异。有趣的是，尽管皮质酮水平升高，但束缚应激对这些行为几乎没有影响。综合来看，这些结果表明SwLo大鼠的探索性寻求刺激和过度警惕的信息收集行为增加，且不依赖于皮质酮水平。这显示了该模型在研究抑郁症和癫痫共病行为影响方面的实用性，并有助于用于识别这种复杂共病的潜在机制或筛选治疗策略。
