Baskin Britahny, Lee Suhjung Janet, Skillen Emma, Wong Katrina, Rau Holly, Hendrickson Rebecca C, Pagulayan Kathleen, Raskind Murray A, Peskind Elaine R, Phillips Paul E M, Cook David G, Schindler Abigail G
VA Northwest Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States.
Front Behav Neurosci. 2021 Dec 22;15:792648. doi: 10.3389/fnbeh.2021.792648. eCollection 2021.
Blast exposure ( 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.
爆炸暴露(高爆炸药引爆)是军人和退伍军人面临的一个主要潜在创伤源,常导致轻度创伤性脑损伤(mTBI)。有爆炸相关mTBI病史的退伍军人通常会出现执行功能障碍(如记忆力改变、心理灵活性缺陷、适应困难),导致日常功能受损和生活质量下降,但潜在机制尚未完全明确,在爆炸动物模型中也未得到充分研究。为了探究爆炸后mTBI导致执行功能缺陷的潜在行为机制,我们在此使用已建立的爆炸mTBI小鼠模型,研究雄性小鼠重复爆炸暴露史如何影响焦虑/强迫样行为结果以及基于操作性奖励学习和行为灵活性范式的食欲性目标导向行为。我们假设雄性小鼠重复爆炸暴露会导致焦虑/强迫样行为结果以及在基于操作性奖励学习和行为灵活性范式中的相应表现缺陷。相反,结果显示寻求奖励和目标导向行为增加,行为灵活性相应降低。我们还报告了与焦虑、强迫和过度觉醒相关的慢性不良行为变化。综合来看,这些数据表明,爆炸后mTBI导致的执行功能潜在缺陷至少部分与强迫性/反应过度增强和行为不灵活性有关,而不仅仅是由于缺乏动机或无法掌握任务参数,这对后续诊断和治疗管理具有重要意义。