Fear modulation by transcranial direct current stimulation

Aim: Despite the potential of exposure-based psychotherapy in the treatment of anxiety disorders, many patients do not show long-term benefits. This has sparked the interest in procedures that could enhance long-term efficacy of exposure-based therapy. Here, we will explore the potential of transcranial direct current stimulation (tDCS) as a non-invasive and innovative neuromodulation method to facilitate the efficacy of exposure-based therapy, using the fear extinction paradigm in mice as an animal model.
Methods: Male C57BL/6J mice were stereotaxically implanted with an electrode holder base. Following one week of recovery, mice were subjected to auditory fear conditioning (5 tone-shock pairings). Subsequently, freely-moving mice were stimulated 2 x 20 min/day (anodal tDCS at 0.2 mA) for five consecutive days. One day after the last stimulation, fear extinction training was performed (40 non-reinforced tone presentations). Fear extinction memory was assessed 1 day (extinction retrieval) and 21 days (spontaneous recovery) post extinction by automated analysis of freezing behavior. In addition, anxiety-like behavior and working memory were determined in the open field test and y-maze spontaneous alternation test.
Results: Under the used experimental conditions, sham stimulated mice showed strong fear extinction that was not susceptible to spontaneous recovery. Moreover, tDCS had no effect on the investigated aspects of fear processing. Finally, the tDCS procedure had no long-term effects on working memory and anxiety-like behavior.
Conclusions: We observed no effect of tDCS on fear processing in mice when a strong fear extinction procedure was used. In future experiments, we will investigate the effect of tDCS on fear processing when applying a weak extinction procedure, and the effect of tDCS on fear processing in mice resistant to fear extinction.