Tryon Sarah C, Sakamoto Iris M, Kellis Devin M, Kaigler Kris F, Wilson Marlene A
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, United States.
Columbia VA Health Care System, Columbia, SC, United States.
Front Behav Neurosci. 2021 Aug 18;15:740313. doi: 10.3389/fnbeh.2021.740313. eCollection 2021.
The inability to extinguish a traumatic memory is a key aspect of post-traumatic stress disorder (PTSD). While PTSD affects 10-20% of individuals who experience a trauma, women are particularly susceptible to developing the disorder. Despite this notable female vulnerability, few studies have investigated this particular resistance to fear extinction observed in females. Similar to humans, rodent models of Pavlovian fear learning and extinction show a wide range of individual differences in fear learning and extinction, although female rodents are considerably understudied. Therefore, the present study examined individual differences in fear responses, including freezing behavior and ultrasonic vocalizations (USVs), of female Long-Evans rats during acquisition of fear conditioning and cued fear extinction. Similar to prior studies in males, female rats displayed individual variation in freezing during cued fear extinction and were divided into extinction competent (EC) and extinction resistant (ER) phenotypes. Differences in freezing between ER and EC females were accompanied by shifts in rearing during extinction, but no darting was seen in any trial. Freezing behavior during fear learning did not differ between the EC and ER females. Vocalizations emitted in the 22 and 50 kHz ranges during fear learning and extinction were also examined. Unlike vocalizations seen in previous studies in males, very few 22 kHz distress vocalizations were emitted by female rats during fear acquisition and extinction, with no difference between ER and EC groups. Interestingly, all female rats produced significant levels of 50 kHz USVs, and EC females emitted significantly more 50 kHz USVs than ER rats. This difference in 50 kHz USVs was most apparent during initial exposure to the testing environment. These results suggest that like males, female rodents show individual differences in both freezing and USVs during fear extinction, although females appear to vocalize more in the 50 kHz range, especially during initial periods of exposure to the testing environment, and emit very few of the 22 kHz distress calls that are typically observed in males during fear learning or extinction paradigms. Overall, these findings show that female rodents display fear behavior repertoires divergent from males.
无法消除创伤性记忆是创伤后应激障碍(PTSD)的一个关键方面。虽然PTSD影响着10%至20%经历过创伤的个体,但女性尤其容易患上这种疾病。尽管女性存在这种明显的易感性,但很少有研究调查女性中观察到的这种对恐惧消退的特殊抵抗力。与人类相似,巴甫洛夫恐惧学习和消退的啮齿动物模型在恐惧学习和消退中表现出广泛的个体差异,尽管对雌性啮齿动物的研究相当不足。因此,本研究考察了雌性长 Evans 大鼠在恐惧条件反射习得和线索性恐惧消退过程中恐惧反应的个体差异,包括僵住行为和超声波发声(USV)。与之前对雄性的研究相似,雌性大鼠在线索性恐惧消退过程中的僵住表现出个体差异,并被分为消退能力强(EC)和消退抵抗(ER)表型。ER和EC雌性大鼠在僵住方面的差异伴随着消退过程中竖毛行为的变化,但在任何试验中都未观察到窜动。EC和ER雌性大鼠在恐惧学习过程中的僵住行为没有差异。还检查了恐惧学习和消退过程中22千赫和50千赫范围内发出的发声。与之前对雄性的研究中观察到的发声不同,雌性大鼠在恐惧习得和消退过程中很少发出22千赫的痛苦叫声,ER组和EC组之间没有差异。有趣的是,所有雌性大鼠都发出了显著水平的50千赫USV,并且EC雌性大鼠发出的50千赫USV比ER大鼠显著更多。这种50千赫USV的差异在最初接触测试环境时最为明显。这些结果表明,与雄性一样,雌性啮齿动物在恐惧消退过程中的僵住和USV方面都表现出个体差异,尽管雌性在50千赫范围内发声更多,尤其是在最初接触测试环境期间,并且发出的22千赫痛苦叫声很少,而在恐惧学习或消退范式中,雄性通常会发出这种叫声。总体而言,这些发现表明雌性啮齿动物表现出与雄性不同的恐惧行为模式。