Effects of repeated anodal transcranial direct current stimulation on auditory fear extinction in C57BL/6J mice

Abstract

Background: Trauma-based psychotherapy is a first line treatment for post-traumatic stress disorder (PTSD) but not all patients achieve long-term remission. Transcranial direct current stimulation (tDCS) received considerable attention as a neuromodulation method that may improve trauma-based psychotherapy. Objective: We explored the effects of repeated anodal tDCS over the prefrontal cortex (PFC) on fear extinction in mice as a preclinical model for trauma-based psychotherapy. Methods: We performed auditory fear conditioning with moderate or high shock intensity on C57BL6/J mice. Next, mice received anodal tDCS (0.2 mA, 20 min) or sham stimulation over the PFC twice daily for five consecutive days. Extinction training was performed by repeatedly exposing mice to the auditory cue the day after the last stimulation session. Early and late retention of extinction were evaluated one day and three weeks after extinction training respectively. Results: We observed no significant effect of tDCS on the acquisition or retention of fear extinction in mice subjected to fear conditioning with moderate intensity. However, when the intensity of fear conditioning was high, tDCS significantly lowered freezing during the acquisition of extinction, regardless of the extinction protocol. Moreover, when tDCS was combined with a strong extinction protocol, we also observed a significant improvement of early extinction recall. Finally, we found that tDCS reduced generalized fear induced by contextual cues when the intensity of conditioning is high and extinction training limited. Conclusions: Our data provide a rationale to further explore anodal tDCS over the PFC as potential support for trauma-based psychotherapy for PTSD.

Anodal tDCS applied to the left frontal cortex abrogates scopolamine-induced fear memory deficit via the dopaminergic system

“…On the other hand, the persistence of fear memory depends on the number of cue-shock pairings and the shock intensity. In a recent study, repeated anodal tDCS had no significant effect on the acquisition or retention of fear extinction in mice subjected to fear conditioning with 0.2 mA foot shock, while it significantly lowered freezing during the acquisition of extinction when the intensity of fear conditioning was 1 mA (Van Schuerbeek et al, 2021). Authors found that tDCS reduced generalized fear induced by contextual cues when the intensity of conditioning is high, and extinction training is limited (Van Schuerbeek et al, 2021).…”

Influence of Stress Severity on Contextual Fear Extinction and Avoidance in a Posttraumatic-like Mouse Model

“…Indeed, we know that extinction learning mostly relies on the top-down control of the vmPFC over the amygdala. Using this model to study new therapeutic approaches that could aim to increase vmPFC activity (e.g., neurostimulation techniques [29,48,56,57]) or enhance fear extinction with molecules known to interact with this inhibitory learning (e.g., curcumin [58,59] or ketamine [60]) might help us find efficient protocols to accompany or even enhance trauma-focused psychotherapies.…”

Exploring Refinement Strategies for Single Housing of Male C57BL/6JRj Mice: Effect of Cage Divider on Stress-Related Behavior and Hypothalamic-Pituitary-Adrenal-Axis Activity

“…The auditory fear conditioning paradigm was used to study fear memory formation as previously described (De Bundel et al, 2016;Van Schuerbeek et al, 2021). The experiments were carried out in a fear conditioning apparatus containing a test box (17 cm width × 17 cm length × 24 cm height) placed within a soundproof chamber (Isolation Cubicle 46000-590, Ugo Basile, Italy).…”