氟西汀和(R,S)氯胺酮对减轻雄性小鼠条件反射恐惧行为的功效

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Megan Wells, Jan Hoffmann, Autumn Stage, Isabella Enger, Jayme Pomper, Lily Briggs, Amber LaCrosse
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引用次数: 0

摘要

创伤后应激障碍(PTSD)是由创伤或应激事件引起的。这种疾病的相关症状包括持续的记忆重现和恐惧泛化。目前针对创伤后应激障碍的药物治疗效果不佳,只有不到 30% 的患者症状得到缓解。本研究旨在确定急性(R,S)氯胺酮和慢性氟西汀(FLX)在减少恐惧记忆和恐惧泛化方面的疗效。在啮齿类动物中,恐惧条件反射(FC)是文献中常用的诱导创伤后应激障碍症状相关行为的方法,而开放场试验(OFT)可以评估探索新环境时的焦虑和恐惧泛化行为。在本研究中,FC 包括一个白噪声提示刺激和四个无法逃脱的脚震。治疗在 FC 4 小时后开始。分别在 24 小时和 2 周后再次接触 FC 刺激时记录恐惧和焦虑行为。OFT 在最后一次 FC 再次暴露前一天进行。结果表明,联合使用急性氯胺酮和慢性 FLX 可以减少 2 周后再次暴露时的恐惧记忆行为,但不能减少 OFT 中的焦虑和恐惧泛化行为。单独使用 FLX 对减少与恐惧泛化有关的行为最为有效。这项研究为现有的有关恐惧记忆和恐惧泛化的恐惧和焦虑行为的药物治疗文献做出了贡献。有必要继续开展研究,以复制研究结果、优化治疗方案并调查分子对创伤和治疗的适应性。意义声明 在美国,多达 6% 的人会在一生中患上创伤后应激障碍,而在目前的治疗方案下,只有不到一半的人能缓解症状。这项研究初步证实了氯胺酮和 FLX 在减少小鼠由恐惧条件反射诱发的创伤后应激障碍类似行为方面的疗效。与目前的标准疗法相比,研究结果表明,氯胺酮和FLX有可能为创伤后应激障碍等压力相关疾病患者提供更有效的治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy of Fluoxetine and (R,S) Ketamine in Attenuating Conditioned Fear Behaviors in Male Mice.

Post-traumatic stress disorder (PTSD) is caused by exposure to a traumatic or stressful event. Symptoms related to this disorder include persistent re-experiencing of memories and fear generalization. Current pharmacological treatments for PTSD are insufficient, with fewer than 30% of patients reporting symptom remission. This study aims to determine the efficacy of acute (R,S) ketamine and chronic fluoxetine (FLX) in reducing fear memory and fear generalization. In rodents, fear conditioning (FC) is commonly used in the literature to induce behaviors related to symptoms of PTSD, and the open field test (OFT) can assess anxiety and fear generalization behaviors during the exploration of a novel environment. In this study, FC consisted of a white noise cue stimulus and four inescapable foot shocks. Treatments began 4 hours after FC. Fear and anxiety behaviors were recorded during re-exposure to the FC stimuli at 24 hours and 2 weeks. The OFT was conducted one day before the last FC re-exposure. Results support the combined use of acute ketamine and chronic FLX as a treatment for reducing behaviors indicative of fear memory during re-exposure at 2 weeks, but not behaviors indicative of anxiety and fear generalization in the OFT. FLX alone was most effective in reducing behaviors related to fear generalization. This study contributes to the existing literature on pharmacological treatment for fear and anxiety behaviors relating to fear memory and fear generalization. Continued research is necessary to replicate results, optimize treatment protocols, and investigate the molecular adaptations to trauma and treatment. Significance Statement Up to 6% of people in the United States will develop PTSD within their lifetime, and less than half of those individuals will find relief from their symptoms given the current therapeutic options. This study offers preliminary support for the efficacy of ketamine and FLX in reducing PTSD-like behaviors induced by fear-conditioning in mice. Compared to current standard treatments, results indicate the potential for a more effective therapeutic option for those with stress-related disorders, such as PTSD.

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来源期刊
CiteScore
6.90
自引率
0.00%
发文量
115
审稿时长
1 months
期刊介绍: A leading research journal in the field of pharmacology published since 1909, JPET provides broad coverage of all aspects of the interactions of chemicals with biological systems, including autonomic, behavioral, cardiovascular, cellular, clinical, developmental, gastrointestinal, immuno-, neuro-, pulmonary, and renal pharmacology, as well as analgesics, drug abuse, metabolism and disposition, chemotherapy, and toxicology.
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