de Souza Camila Pasquini, Gambeta Eder, Stern Cristina Aparecida Jark, Zanoveli Janaína Menezes
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil.
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil.
Behav Brain Res. 2019 Feb 1;359:749-754. doi: 10.1016/j.bbr.2018.09.008. Epub 2018 Sep 13.
Anxiety and stress disorders, such as posttraumatic stress disorder (PTSD) have been described as debilitating comorbidities of diabetes. In the present study, we aimed to investigate anxiety-like behavior and the extinction and generalization of aversive memories in fear conditioning using a streptozotocin-induced model of diabetes (DBT). Moreover, considering that DBT animals present increased oxidative stress in brain areas related to anxiety and memory, we aimed to evaluate the effect of prolonged treatment with antioxidant vitamin E on behavioral parameters of anxiety and fear memory and on the diabetic condition. It was observed that DBT animals showed a deficiency in extinguishing the aversive memory in a fear conditioning test, along with a generalization of the fear memory. They also present a more pronounced anxiety-like behavior in the elevated plus maze test. VIT E treatment (300 mg/kg, p.o.) was not able to reduce hyperglycemia; however, it was able to block the anxiogenic-like behavior, also improving the deficit in the extinction of the aversive memory as well as blocking the generalization of such memory in a different context. Taken together, our data suggest that DBT animals are prone to extinction deficits and generalization of fear memories, behaviors which are observed in models of PTSD. Lastly, prolonged VIT E supplementation may be effective in the treatment of anxiety, extinction deficit and generalization of fear memories induced by the diabetic condition.
焦虑和应激障碍,如创伤后应激障碍(PTSD),已被描述为糖尿病的使人衰弱的合并症。在本研究中,我们旨在使用链脲佐菌素诱导的糖尿病模型(DBT),研究恐惧条件反射中焦虑样行为以及厌恶记忆的消退和泛化。此外,考虑到DBT动物在与焦虑和记忆相关的脑区表现出氧化应激增加,我们旨在评估抗氧化剂维生素E长期治疗对焦虑和恐惧记忆行为参数以及糖尿病状况的影响。观察到DBT动物在恐惧条件反射测试中表现出厌恶记忆消退缺陷以及恐惧记忆泛化。它们在高架十字迷宫测试中也表现出更明显的焦虑样行为。维生素E治疗(300mg/kg,口服)不能降低高血糖;然而,它能够阻断焦虑样行为,还能改善厌恶记忆消退缺陷,并在不同背景下阻断这种记忆的泛化。综上所述,我们的数据表明,DBT动物容易出现消退缺陷和恐惧记忆泛化,这些行为在PTSD模型中也有观察到。最后,长期补充维生素E可能对治疗糖尿病引起的焦虑、消退缺陷和恐惧记忆泛化有效。