Abstract
Exposure-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.
Highlights
Post-traumatic stress disorder (PTSD) affects 22.4 million Americans and can develop following highly stressful experiences, such as combat or sexual assault.[1]
These findings suggest that Vagus nerve stimulation (VNS) might be effective in enhancing extinction memory in a rat model of PTSD
During a 10-min test, time spent in the open arms, time spent in the closed arms and time spent in the center of the maze were recorded
Summary
Post-traumatic stress disorder (PTSD) affects 22.4 million Americans and can develop following highly stressful experiences, such as combat or sexual assault.[1]. Exposure-based therapies are considered the gold standard of treatment for PTSD.[6] The goal of exposure-based therapies is to replace conditioned associations of the trauma with new, more appropriate associations. These therapies are based on Pavlov’s observations that learned associations can be modified with extinction training.[7] Despite their demonstrated therapeutic efficacy, exposure-based therapies for PTSD have high nonresponse and dropout rates.[8,9,10] PTSD patients appear to be resistant to exposure-based therapies because of a generalized extinction deficit.[11,12,13,14] Further, PTSD patients are impaired in their ability to extinguish conditioned fears that are acquired in controlled laboratory studies.[12,15,16] Adjuvant treatments that improve the consolidation of extinction learning may improve the effectiveness of exposure-based therapies.
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