Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States; School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Exp Neurol. 2021 Jul;341:113718. doi: 10.1016/j.expneurol.2021.113718. Epub 2021 Apr 15.
Studies in rodents indicate that pairing vagus nerve stimulation (VNS) with extinction training enhances fear extinction. However, the role of stimulation parameters on the effects of VNS remains largely unknown. Identifying the optimal stimulation intensity is a critical step in clinical translation of neuromodulation-based therapies. Here, we sought to investigate the role of stimulation intensity in rats receiving VNS paired with extinction training in a rat model for Posttraumatic Stress Disorder (PTSD). Male Sprague-Dawley rats underwent single prolonged stress followed by a severe fear conditioning training and were implanted with a VNS device. After recovery, independent groups of rats were exposed to extinction training paired with sham (0 mA) or VNS at different intensities (0.4, 0.8, or 1.6 mA). VNS intensities of 0.4 mA or 0.8 mA decreased conditioned fear during extinction training compared to sham stimulation. Pairing extinction training with moderate VNS intensity of 0.8 mA produced significant reduction in conditioned fear during extinction retention when rats were tested a week after VNS-paired extinction. High intensity VNS at 1.6 mA failed to enhance extinction. These findings indicate that a narrow range of VNS intensities enhances extinction learning, and suggest that the 0.8 mA VNS intensity used in earlier rodent and human stroke studies may also be the optimal in using VNS as an adjuvant in exposure therapies for PTSD.
在啮齿动物中的研究表明，将迷走神经刺激 (VNS) 与消退训练相结合可以增强恐惧消退。然而，刺激参数对 VNS 效果的影响在很大程度上仍然未知。确定最佳刺激强度是神经调节为基础的治疗方法在临床转化中的关键步骤。在这里，我们试图在创伤后应激障碍 (PTSD) 的大鼠模型中研究刺激强度在接受 VNS 与消退训练相结合的大鼠中的作用。雄性 Sprague-Dawley 大鼠接受单次延长应激，然后进行严重的恐惧条件训练，并植入 VNS 装置。恢复后，独立的大鼠组接受与假刺激 (0 mA) 或不同强度的 VNS (0.4、0.8 或 1.6 mA) 相结合的消退训练。与假刺激相比，0.4 mA 或 0.8 mA 的 VNS 强度在消退训练期间降低了条件性恐惧。当大鼠在 VNS 配对消退后一周进行测试时，将消退训练与中等强度的 0.8 mA 的 VNS 配对可显著减少消退保留期间的条件性恐惧。1.6 mA 的高强度 VNS 未能增强消退。这些发现表明，狭窄范围的 VNS 强度增强了消退学习，并表明在早期啮齿动物和人类中风研究中使用的 0.8 mA VNS 强度也可能是将 VNS 用作 PTSD 暴露疗法的辅助剂的最佳强度。
