Departments of Biology and Neuroscience & Behavior, Barnard College of Columbia University, 3009 Broadway, New York, NY, 10027, United States.
Neuropharmacology. 2023 Jan 1;222:109298. doi: 10.1016/j.neuropharm.2022.109298. Epub 2022 Oct 31.
Women have increased vulnerability to PTSD and anxiety disorders compared to men. Understanding the neurobiological underpinnings of these disorders is critical for identifying risk factors and developing appropriate sex-specific interventions. Despite the clear clinical relevance of an examination of sex differences in fear responses, the vast majority of pre-clinical research on fear learning and memory formation has exclusively used male animals. This review highlights sex differences in context and cued fear conditioning, fear extinction and fear generalization with a focus on the neural circuits underlying these behaviors in rodents. There are mixed reports of behavioral sex differences in context and cued fear conditioning paradigms, which can depend upon the behavioral indices of fear. However, there is greater evidence of differential activation of the hippocampus, amygdalar nuclei and the prefrontal cortical regions in male and female rodents during context and cued fear conditioning. The bed nucleus of the stria terminalis (BNST), a sexually dimorphic structure, is of particular interest as it differentially contributes to fear responses in males and females. In addition, while the influence of the estrous cycle on different phases of fear conditioning is delineated, the clearest modulatory effect of estrogen is on fear extinction processes. Examining the variability in neural responses and behavior in both sexes should increase our understanding of how that variability contributes to the neurobiology of affective disorders. This article is part of the Special Issue on 'Fear, anxiety and PTSD'.
与男性相比，女性更容易患上创伤后应激障碍和焦虑症。了解这些疾病的神经生物学基础对于确定风险因素和开发针对性别的干预措施至关重要。尽管研究恐惧反应中的性别差异具有明显的临床意义，但绝大多数关于恐惧学习和记忆形成的临床前研究都仅使用雄性动物。这篇综述强调了在情境和线索恐惧条件作用、恐惧消退和恐惧泛化方面的性别差异，重点介绍了啮齿动物中这些行为的神经回路。在情境和线索恐惧条件作用范式中，行为存在混合的性别差异报告，这可能取决于恐惧的行为指标。然而，有更多证据表明，在情境和线索恐惧条件作用期间，雄性和雌性啮齿动物的海马体、杏仁核核和前额叶皮质区域的激活存在差异。终纹床核（BNST）是一种性别二态性结构，它在雄性和雌性的恐惧反应中有着特别的作用。此外，虽然已经描述了发情周期对不同阶段的恐惧条件作用的影响，但雌激素最明显的调节作用是在恐惧消退过程中。研究两性的神经反应和行为的可变性应该会增加我们对这种可变性如何导致情感障碍的神经生物学的理解。本文是“恐惧、焦虑和 PTSD”特刊的一部分。
