ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) PROMOTES ANTIDEPRESSANT EFFECTS AND MODULATES SEROTONERGIC ACTIVITY BY ENGAGING THE PREFRONTAL–DORSAL RAPHE CIRCUIT IN MICE

The medial prefrontal cortex (mPFC)-dorsal raphe dorsal nucleus (DRD) circuit is involved in various brain functions. In Major Depressive Disorder (MDD), this circuit is dysregulated, showing altered mPFC activity and decreased serotonin (5-HT) levels. In recent years, prefrontal anodal transcranial direct current stimulation (A-tDCS) has emerged as a promising antidepressant treatment, potentially modulating the 5-HT tone. Here, we investigate the impact of A-tDCS on the mPFC-DRD network. Young female C57BL/6 mice received either a single A-tDCS session or daily sessions for five consecutive days to evaluate short- (48 hours) and long-term (30 days) effects. Subsequent analyses included quantification of 5-HT and related metabolites, local field potential (LFP) recordings in mPFC and DRD, extracellular single-unit (SU) in vivo recordings of 5-HT neurons, and a forced swim test (FST), followed by histological analysis. Acute A-tDCS treatment showed a tendency towards an increased number of c-Fos+ and c-Fos+Tph-2+ neurons in the DRD. Repeated stimulation raised the long-term levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA) in the midbrain. Additionally, SU recordings showed a higher firing rate of 5-HT neurons in A-tDCS mice. Moreover, LFP recordings revealed a transient reduction trend of mPFC-DRD coherence in stimulated mice. Finally, A-tDCS reduced the immobility time in the FST at both time points, along with a trend towards a decreased number of DRD cFos+ and cFos+Tph-2+ neurons. Our results indicate that prefrontal A-tDCS exerts both short- and long-term antidepressant-like effects in mice, in parallel with mPFC–DRD circuit modulation.