Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice.
Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice.
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DOI：
10.3389/fnbeh.2021.792648
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发表时间：
2021
影响因子：
3
通讯作者：
Schindler AG
中科院分区：
文献类型：
--
作者：
Baskin B;Lee SJ;Skillen E;Wong K;Rau H;Hendrickson RC;Pagulayan K;Raskind MA;Peskind ER;Phillips PEM;Cook DG;Schindler AG
爆炸暴露（通过高爆炸物的爆炸）是军人和退伍军人的主要潜在创伤源，通常导致轻度创伤性脑损伤（mTBI）。执行功能障碍（例如，记忆力改变、精神灵活性缺陷、适应性困难）通常由具有爆炸相关mTBI病史的退伍军人报告，导致日常功能受损和生活质量下降，但潜在机制尚未完全理解，并且尚未在爆炸动物模型中进行充分研究。为了研究潜在的潜在的行为机制，导致执行功能缺陷后爆炸mTBI，在这里，我们研究了历史的重复爆炸暴露在雄性小鼠如何影响焦虑/强迫症样的结果和食欲目标导向的行为，使用一个既定的小鼠模型爆炸mTBI。我们假设雄性小鼠反复暴露于爆炸声中会导致焦虑/强迫样结果，并在基于操作的奖励学习和行为灵活性范式中出现相应的表现缺陷。相反，结果表明，奖励寻求和目标导向的行为和一致的行为灵活性下降的增加。我们还报告了与焦虑、强迫性和过度觉醒相关的慢性不良行为变化。总之，这些数据表明，急性mTBI后执行功能的潜在缺陷至少部分与增强的强迫性/高反应性和行为敏感性有关，而不仅仅是由于缺乏动力或无法获得任务参数，这对后续诊断和治疗管理具有重要意义。
Blast exposure (via detonation of high explosives) represents a major potential trauma source for Servicemembers and Veterans, often resulting in mild traumatic brain injury (mTBI). Executive dysfunction (e.g., alterations in memory, deficits in mental flexibility, difficulty with adaptability) is commonly reported by Veterans with a history of blast-related mTBI, leading to impaired daily functioning and decreased quality of life, but underlying mechanisms are not fully understood and have not been well studied in animal models of blast. To investigate potential underlying behavioral mechanisms contributing to deficits in executive functioning post-blast mTBI, here we examined how a history of repetitive blast exposure in male mice affects anxiety/compulsivity-like outcomes and appetitive goal-directed behavior using an established mouse model of blast mTBI. We hypothesized that repetitive blast exposure in male mice would result in anxiety/compulsivity-like outcomes and corresponding performance deficits in operant-based reward learning and behavioral flexibility paradigms. Instead, results demonstrate an increase in reward-seeking and goal-directed behavior and a congruent decrease in behavioral flexibility. We also report chronic adverse behavioral changes related to anxiety, compulsivity, and hyperarousal. In combination, these data suggest that potential deficits in executive function following blast mTBI are at least in part related to enhanced compulsivity/hyperreactivity and behavioral inflexibility and not simply due to a lack of motivation or inability to acquire task parameters, with important implications for subsequent diagnosis and treatment management.