Minshall Brianna L, Wasylyshyn Catherine F, Brand Kate M, Bartoszek Caroline M, Seipel Kennedy A, Booms Madeline M, Chappell Lucy C, Reichert Amanda N, Dowell Jacob R, Buck Angeles L, Beckett Henry T, Lowry Christopher A, Quinn Jennifer J
Department of Psychology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA.
Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
Brain Sci. 2024 Dec 21;14(12):1287. doi: 10.3390/brainsci14121287.
BACKGROUND/OBJECTIVES: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown. PTSD involves a complex network of highly interconnected brain regions, including the bed nucleus of the stria terminalis (BNST). Serotonin (5-HT) release into the BNST yields an increased expression of both fear and anxiety, specifically through 5-HT receptor signaling. The present experiment addressed whether 5-HT receptor signaling in the BNST is necessary for the acquisition of early-life stress (ELS)-induced enhancements in adult contextual fear learning.
Rats received 0 or 15 footshocks on postnatal day 17, an established model of acute ELS (aELS) that yields enhanced adult fear learning. In adulthood, rats received bilateral infusions of a vehicle, a 5-HT receptor antagonist (RS-102221), or a 5-HT receptor agonist (MK-212) into the BNST 15 min prior to one-footshock contextual fear conditioning in a novel context. The next day, rats were returned to the fear-conditioning context to assess their fear memory (freezing).
Females demonstrated aELS-induced enhancement in contextual fear learning, while males did not. BNST infusions of RS-102221 reduced contextual fear conditioning, independent of aELS condition and sex. Infusions of MK-212 had no effect.
Taken together, these data suggest that serotonergic signaling through 5-HT receptors in the BNST contributes to contextual fear conditioning, but not aELS-induced stress-enhanced fear learning (SEFL).
背景/目的：啮齿动物为恐惧和焦虑相关行为提供了一个有用的转化模型。先前受到应激的动物表现出的生理和行为应激反应与焦虑人类中观察到的反应相似。被诊断患有创伤后应激障碍（PTSD）的患者会出现一系列使人衰弱的焦虑症状，这些症状是由暴露于一个或多个创伤性事件引起的，早期经历过不良事件的个体以及女性被诊断为PTSD的易感性增加；然而，这种易感性增加的机制仍然未知。PTSD涉及一个由高度相互连接的脑区组成的复杂网络，包括终纹床核（BNST）。血清素（5-HT）释放到BNST中会导致恐惧和焦虑的表达增加，具体是通过5-HT受体信号传导。本实验探讨了BNST中的5-HT受体信号传导对于获得早期生活应激（ELS）诱导的成年情境恐惧学习增强是否必要。
大鼠在出生后第17天接受0次或15次足部电击，这是一种已建立的急性ELS（aELS）模型，可产生增强的成年恐惧学习。成年后，大鼠在新环境中进行单足部电击情境恐惧条件反射前15分钟，双侧向BNST注入载体、5-HT受体拮抗剂（RS-102221）或5-HT受体激动剂（MK-212）。第二天，将大鼠放回恐惧条件反射环境中以评估它们的恐惧记忆（僵住）。
雌性大鼠表现出aELS诱导的情境恐惧学习增强，而雄性大鼠则没有。向BNST注入RS-102221可降低情境恐惧条件反射，与aELS条件和性别无关。注入MK-212没有效果。
综上所述，这些数据表明，通过BNST中的5-HT受体进行的血清素能信号传导有助于情境恐惧条件反射，但对aELS诱导的应激增强恐惧学习（SEFL）没有作用。
