Vagus Nerve Stimulation Promotes Generalization of Conditioned Fear Extinction and Reduces Anxiety in Rats

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dc.contributor.ORCID0000-0003-4225-241X (Hays, SA)
dc.contributor.VIAF13146094343400332984 (Hays, SA)
dc.contributor.authorNoble, Lindsey J.
dc.contributor.authorMeruva, Venkat B.
dc.contributor.authorHays, Seth A.
dc.contributor.authorRennaker, Robert L.
dc.contributor.authorKilgard, Michael P.
dc.contributor.authorMcIntyre, Christa K.
dc.contributor.utdAuthorNoble, Lindsey J.
dc.contributor.utdAuthorMeruva, Venkat B.
dc.contributor.utdAuthorHays, Seth A.
dc.contributor.utdAuthorRennaker, Robert L.
dc.contributor.utdAuthorKilgard, Michael P.
dc.contributor.utdAuthorMcIntyre, Christa K.
dc.date.accessioned2020-07-09T19:35:44Z
dc.date.available2020-07-09T19:35:44Z
dc.date.issued2018-09-21
dc.description.abstractBackground: Exposure-based therapies are used to treat a variety of trauma- and anxiety-related disorders by generating successful extinction following cue exposure during treatment. The development of adjuvant strategies that accelerate extinction learning, improve tolerability, and increase efficiency of treatment could increase the efficacy of exposure-based therapies. Vagus nerve stimulation (VNS) paired with exposure can enhance fear extinction, in rat models of psychiatric disorders, and chronic administration of VNS reduces anxiety in rats and humans. Objective: We tested whether VNS, like other cognitive enhancers, could produce generalization of extinction for stimuli that are not presented during the extinction sessions, but are associated with the fear event. Methods: Male Sprague Dawley rats underwent auditory fear conditioning with two easily discriminable auditory stimuli. Following fear conditioning, extinction training consisted of exposure to only one of the conditioned sounds. Half of the rats received VNS and half received sham stimulation during with sound presentations. VNS effects on anxiety were examined in a separate study where VNS was administered prior to testing on the elevated plus maze. Results: Sham stimulated rats given 20 presentations of a conditioned stimulus (CS) during the extinction session showed performance that was matched to VNS-treated rats given only 4 presentations of the CS. Despite comparable levels of freezing to the presented CS, only the VNS-treated rats showed a significant decrease in freezing to the CS that was not presented. VNS-induced generalization of extinction was observed only when the two sounds were paired with footshock within the same fear conditioning session; VNS did not promote generalization of extinction when the two sounds were conditioned on different days or in different contexts. On the anxiety test, VNS administration significantly increased time spent in the open arms of the elevated plus maze. Conclusion: These results provide evidence that VNS can promote generalization of extinction to other stimuli associated with a specific fear experience. Furthermore, non-contingent VNS appears to reduce anxiety. The ability to generalize extinction and reduce anxiety makes VNS a potential candidate for use as an adjunctive strategy to improve the efficacy and tolerability of exposure-based therapies.
dc.description.departmentSchool of Behavioral and Brain Sciences
dc.description.departmentErik Jonsson School of Engineering and Computer Science
dc.description.departmentTexas Biomedical Device Center
dc.description.sponsorshipDefense Advanced Research Projects Agency Biological Technologies Office (BTO) Electrical Prescriptions (ElectRx) program under the auspices of Dr. Doug Weber and Dr. Eric Van Gieson and 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, MH099655.
dc.identifier.bibliographicCitationNoble, Lindsey J., Venkat B. Meruva, Seth A. Hays, Robert L. Rennaker, et al. 2019. "Vagus nerve stimulation promotes generalization of conditioned fear extinction and reduces anxiety in rats." Brain Stimulation 12: 9-18, doi: 10.1016/j.brs.2018.09.013
dc.identifier.issn1935-861X
dc.identifier.urihttp://dx.doi.org/10.1016/j.brs.2018.09.013
dc.identifier.urihttps://hdl.handle.net/10735.1/8697
dc.identifier.volume12
dc.language.isoen
dc.publisherElsevier Science Inc
dc.rights©2018 Elsevier Inc. All rights reserved.
dc.source.journalBrain Stimulation
dc.subjectVagus nerve
dc.subjectAnxiety
dc.subjectFear
dc.subjectExposure therapy
dc.subjectMemory
dc.subjectPlasticity
dc.subjectNoradrenaline
dc.subject.meshVagus Nerve Stimulation
dc.subject.meshBrain-Derived Neurotrophic Factor
dc.subject.meshNorepinephrine
dc.titleVagus Nerve Stimulation Promotes Generalization of Conditioned Fear Extinction and Reduces Anxiety in Rats
dc.type.genrearticle

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McIntyre-Rodriguez, Christa
Hays, Seth
Kilgard, Michael P.
Rennaker, Robert L.