Tumolo Jessica M, Kutlu Munir Gunes, Gould Thomas J
Department of Psychology, Temple University, Philadelphia, PA, USA.
The Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA.
Behav Brain Res. 2018 Apr 2;341:176-180. doi: 10.1016/j.bbr.2018.01.002. Epub 2018 Jan 5.
Post-traumatic stress disorder (PTSD) is a devastating disorder with symptoms such as flashbacks, hyperarousal, and avoidance of reminders of the traumatic event. Exposure therapy, which attempts to extinguish fear responses, is a commonly used treatment for PTSD but relapse following successful exposure therapy is a frequent problem. In rodents, spontaneous recovery (SR), where extinguished fear responses resurface following extinction treatment, is used as a model of fear relapse. Previous studies from our lab showed that chronic nicotine impaired fear extinction and acute nicotine enhanced SR of contextual fear in adult male mice. In addition, we showed that acute nicotine's effects were specific to SR as acute nicotine did not affect recall of contextual fear conditioning in the absence of extinction. However, effects of chronic nicotine administration on SR are not known. Therefore, in the present study, we investigated if chronic nicotine administration altered SR or recall of contextual fear in adult male and female C57BL/6J mice. Our results showed that chronic nicotine significantly enhanced SR in female mice and significantly decreased SR in males. Chronic nicotine had no effect on recall of contextual fear in males or females. Female sham mice also had significantly less baseline SR than male sham mice. Overall, these results demonstrate sex differences in SR of fear memories and that chronic nicotine modulates these effects on SR but nicotine does not alter recall of contextual fear.
创伤后应激障碍（PTSD）是一种破坏性疾病，具有闪回、过度警觉以及回避创伤事件提示物等症状。暴露疗法试图消除恐惧反应，是治疗PTSD常用的方法，但成功的暴露疗法后复发是一个常见问题。在啮齿动物中，自发恢复（SR），即消退治疗后消退的恐惧反应重新出现，被用作恐惧复发的模型。我们实验室之前的研究表明，慢性尼古丁损害恐惧消退，急性尼古丁增强成年雄性小鼠情境恐惧的自发恢复。此外，我们表明急性尼古丁的作用对自发恢复具有特异性，因为在没有消退的情况下，急性尼古丁不影响情境恐惧条件反射的回忆。然而，慢性尼古丁给药对自发恢复的影响尚不清楚。因此，在本研究中，我们调查了慢性尼古丁给药是否会改变成年雄性和雌性C57BL/6J小鼠的自发恢复或情境恐惧的回忆。我们的结果表明，慢性尼古丁显著增强雌性小鼠的自发恢复，显著降低雄性小鼠的自发恢复。慢性尼古丁对雄性或雌性小鼠情境恐惧的回忆没有影响。雌性假手术小鼠的基线自发恢复也明显少于雄性假手术小鼠。总体而言，这些结果证明了恐惧记忆自发恢复中的性别差异，并且慢性尼古丁调节对自发恢复的这些影响，但尼古丁不会改变情境恐惧的回忆。
