Designer receptors exclusively activated by designer drugs (DREADDs) used for endophenoptyping neuronal networks of depression by functional connectivity magnetic resonance imaging (fc-fMRI)
Final Report Abstract
In summary, our study using DREADD activation of the lateral habenula and investigating changes in functional brain networks using a longitudinal design, confirmed the key role of LHb in the modulation of DMN and depressive-like neural brain network reorganization. More importantly, our study revealed that short- and long-term activation of the LHb leads to different DMN networks. While the short-term activation showed hyperfunctional DMN networks, rats with long-term activation of LHb leads to a hypofunctional DMN. We speculate that this discrepancy of the DMN network between short and repeated LHb activation might be driven by depressive illness durations and stage. In support of our hypothesis, a recent human rsfMRI-meta-study reported that reduced functional connectivity in DMN was only found in recurrent MDD, not in first-episode drug-naïve MDD patients. Those questions should be addressed in the follow-up research. Nevertheless, our results suggest that the LHb should be a prime target for further MDD research, especially to explore, which neuroprojections provide the antidepressant effect, and mediate symptomatic improvement.
