Impaired reversal learning in an animal model of anorexia nervosa
Impaired reversal learning in an animal model of anorexia nervosa
复制标题
DOI：
10.1016/j.physbeh.2017.06.013
复制
发表时间：
2017-10-01
影响因子：
2.9
通讯作者：
Kocsis, Bernat
中科院分区：
文献类型：
--
作者：
Allen, Patricia J.;Jimerson, David C.;Kocsis, Bernat
背景：临床研究表明神经性厌食症（AN）与认知灵活性受损有关。基于活动的厌食症 (ABA) 是 AN 的一种啮齿动物行为模型，其特征是强迫性的跑轮运动，并伴有自愿的食物限制和渐进的体重减轻。本研究的目的是测试 ABA 是否与认知灵活性受损相关。方法：训练雌性 Sprague-Dawley 大鼠进行注意力设定转移测试 (ASST)，以评估认知灵活性，包括设定转移和逆转学习的能力。大鼠被分配到 ABA 或减肥配对对照 (WPC) 条件下。基线测试后，ABA 组每天可以进食 1 小时，每天可以使用跑轮 23 小时，直到自愿减轻 20% 的体重。对于 WPC 组，跑步轮被锁定，食物的获取受到限制，以与 ABA 组相同的速度减轻体重。在减肥后评估 ASST 表现，并在体重恢复后再次评估。结果：与基线相比，ABA 组（但不是 WPC 组）在低体重时表现出逆转学习显着下降，但在体重恢复后恢复到基线表现。 ASST 的其他组成部分不受影响。结论：ABA 模型中逆转学习受损，表明持续反应增加，揭示了其重现 AN 中皮质功能障碍的选择性组成部分的潜力。这一发现支持 ABA 模型在研究此类缺陷背后的神经机制中的实用性。逆转学习依赖于涉及眶额皮层的神经回路，因此结果暗示了类 AN 状态下的眶额异常。
Background: Clinical investigations indicate that anorexia nervosa (AN) is associated with impaired cognitive flexibility. Activity-based anorexia (ABA), a rodent behavioral model of AN, is characterized by compulsive wheel running associated with voluntary food restriction and progressive weight loss. The goal of this study was to test whether ABA is associated with impaired cognitive flexibility.Methods: Female Sprague-Dawley rats were trained to perform the attentional set-shifting test (ASST) to assess cognitive flexibility, including capacity for set-shifting and reversal learning. Rats were assigned to ABA or weight-loss paired control (WPC) conditions. Following baseline testing, the ABA group had access to food for 1 h/d and access to running wheels 23 h/d until 20% weight loss was voluntarily achieved. For the WPC group, running wheels were locked and access to food was restricted to reduce body weight at the same rate as the ABA group. ASST performance was assessed after weight loss, and again following weight recovery.Results: Compared to baseline, the ABA group (but not the WPC group) showed a significant decrement in reversal learning at low weight, with return to baseline performance following weight restoration. The other components of ASST were not affected.Conclusions: Impaired reversal learning, indicative of increased perseverative responding, in the ABA model reveals its potential to recapitulate selective components of cortical dysfunction in AN. This finding supports the utility of the ABA model for investigations of the neural mechanisms underlying such deficits. Reversal learning relies on neural circuits involving the orbitofrontal cortex and thus the results implicate orbitofrontal abnormalities in AN-like state.