The Effects of Vagus Nerve Stimulation on Extinction of Conditioned Fear

Extinction of conditioned fear is the basis for exposure-based therapies that are used to treat disorders including posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and specific phobias. Though exposure-based therapies are the best evidence-based treatment for anxiety-related disorders, nonresponse and dropout rates are still as high as fifty percent. Failure during or after treatment could stem from generalized extinction impairments seen in patients with PTSD, OCD, and specific phobias. Adjuvant treatments that could enhance extinction of conditioned fear, and improve treatment tolerability would be useful in improving treatment outcomes for patients with anxiety-related disorders. Vagus nerve stimulation (VNS) has been safely used in tens of thousands of patients for epilepsy and treatment resistant depression since FDA approval in 1997. VNS enhances memory consolidation in rats and in humans, and can also enhance extinction of conditioned fear in healthy rats. Here, we expand findings regarding VNS and fear extinction. We found that VNS can enhance extinction of fear in a rat model of PTSD that is resistant to extinction, as well as reduce the incidence of relapse and reverse PTSD-like symptoms including avoidance and heightened anxiety more than one week following treatment. We also found that VNS can generate more broad extinction learning by promoting generalization of extinction of conditioned fear. Though VNS is anxiolytic, our findings also indicate that the mechanism by which VNS enhances extinction of conditioned fear is not through a reduction in anxiety. Taken together, our findings indicate that VNS could be a useful adjunct for exposure-based therapies to improve treatment outcomes by enhancing extinction, and improve tolerability by reducing anxiety.