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. 2017 Aug 22;7(8):e1217. doi: 10.1038/tp.2017.191

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Copyright © 2017 The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Conditioned fear responding across extinction days. (a) VNS treatment reverses maladaptive fear seen in PTSD model rats. Following 11 consecutive days of extinction, rats exposed to the SPS procedure 1 week before AFC (PTSD model rats) did not reach remission of fear. A single, unpaired reminder of the unconditioned stimulus was sufficient to reinstate conditioned fear to the level of freezing measured on the first day of extinction in the PTSD model. PTSD model rats given VNS reached remission of fear by the end of treatment. VNS also attenuated the reinstatement of conditioned fear. Freezing in rats given VNS was significantly reduced compared with freezing on the first day of extinction. PTSD model rats given VNS showed significantly less fear than sham-treated rats on extinction day 5 (**P<0.01) and extinction days 7, 9 and 11 (****P<0.0001). PTSD model rats given VNS showed reduced reinstatement of conditioned fear versus sham-treated rats (****P<0.0001). (b) VNS treatment accelerates extinction in control rats subjected to AFC alone. All rats that underwent AFC alone reached remission of fear by the end of extinction. VNS led to more rapid remission of fear than sham stimulation. VNS-treated rats showed reduced freezing versus sham-treated rats on extinction day 5 (***P<0.001) and extinction day 7 (*P<0.05). AFC alone rats alone did not show complete reinstatement of conditioned fear following a reminder of the unconditioned stimulus. AFC, auditory fear conditioning; PTSD, post-traumatic stress disorder; SPS, single prolonged stress; VNS, vagus nerve stimulation.