Effects of Vagus Nerve Stimulation on Extinction of Conditioned Fear and Post-Traumatic Stress Disorder Symptoms in Rats

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dc.contributor.authorNoble, Lindsey J.en_US
dc.contributor.authorGonzalez, I. J.en_US
dc.contributor.authorMeruva, V. B.en_US
dc.contributor.authorCallahan, Kathleen A.en_US
dc.contributor.authorBelfort, Benjamin D.en_US
dc.contributor.authorRamanathan, K. R.en_US
dc.contributor.authorMeyers, Ericen_US
dc.contributor.authorKilgard, Michael P.en_US
dc.contributor.authorRennaker, Robert L.en_US
dc.contributor.authorMcIntyre, Christa K.en_US
dc.contributor.utdAuthorNoble, Lindsey J.en_US
dc.contributor.utdAuthorGonzalez, I. J.en_US
dc.contributor.utdAuthorMeruva, V. B.en_US
dc.contributor.utdAuthorCallahan, Kathleen A.en_US
dc.contributor.utdAuthorBelfort, Benjamin D.en_US
dc.contributor.utdAuthorRamanathan, K. R.en_US
dc.contributor.utdAuthorMeyers, Ericen_US
dc.contributor.utdAuthorKilgard, Michael P.en_US
dc.contributor.utdAuthorRennaker, Robert L.en_US
dc.contributor.utdAuthorMcIntyre, Christa K.en_US
dc.date.accessioned2018-08-31T14:57:57Z
dc.date.available2018-08-31T14:57:57Z
dc.date.created2017-08-22
dc.description.abstractExposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.en_US
dc.description.departmentSchool of Behavioral and Brain Sciencesen_US
dc.description.sponsorship"This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) Electrical Prescriptions (ElectRx) program under the auspices of Dr Doug Weber through the Space and Naval Warfare Systems Center, Pacific. Grant/Contract No. DARPA-BAA-14-38 and DARPA-BAA-15-06 and by the NIMH, MH105014."en_US
dc.identifier.bibliographicCitationNoble, L. J., I. J. Gonzalez, V. B. Meruva, K. A. Callahan, et al. 2017. "Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats." 7, doi:10.1038/tp.2017.191en_US
dc.identifier.issn2158-3188en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6036
dc.identifier.volume7en_US
dc.language.isoenen_US
dc.relation.urihttp://dx.doi.org/10.1038/tp.2017.191en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalTranslational Psychiatryen_US
dc.subjectAnxiety Disordersen_US
dc.subjectBasolateral Nuclear Complexen_US
dc.subjectDiagnostic and statistical manual of mental disordersen_US
dc.subjectPlasticityen_US
dc.subjectPrefrontal cortexen_US
dc.subjectPost-traumatic stress disorderen_US
dc.subjectLong-term memoryen_US
dc.subjectPsychiatric disordersen_US
dc.titleEffects of Vagus Nerve Stimulation on Extinction of Conditioned Fear and Post-Traumatic Stress Disorder Symptoms in Ratsen_US
dc.typeTexten_US
dc.type.genrearticleen_US

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