University of California at San Francisco, San Francisco, California 94143, USA.
San Francisco Veterans Affairs Health Care System, San Francisco, California 94121, USA.
Learn Mem. 2022 Sep 6;29(9):332-339. doi: 10.1101/lm.053597.122. Print 2022 Sep.
Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.
性别在涉及恐惧条件反射和消退的神经生物学机制中存在差异，这可能导致女性比男性更容易患上创伤后应激障碍（PTSD）。研究表明，生殖激素，如雌二醇，有助于促进恐惧条件反射和消退学习，这可以解释其中的一些差异。然而，常用的激素避孕药对恐惧条件反射和消退的神经生物学机制的影响还知之甚少。本实验室研究对有创伤史的男性和女性，以及患有完全或部分创伤后应激障碍的患者进行了研究，以考察性别和激素避孕的使用对恐惧条件反射、恐惧消退学习和消退保持的影响。参与者接受了带有或不带有电击的刺激（CS+或 CS-）配对的恐惧条件反射。72 小时后进行消退学习，1 周后进行消退保持测试。与未服用激素避孕药的女性和男性相比，服用激素避孕药的女性表现出恐惧条件反射的获得增强和恐惧的消退增强。虽然临床意义尚未确定，但这些结果表明，激素避孕药可能有助于在恐惧获得和消退过程中促进学习。了解性别和激素对恐惧条件反射和消退过程的影响，可能会深入了解创伤后应激障碍的病理生理学，并导致针对不同性别的治疗进展。
