Converging pathways: shared brain circuitry engaged by monoaminergic antidepressants, ketamine and psilocybin

The monoaminergic hypothesis of depression

This research preprint investigates the effects of different antidepressant treatments on brain activity in mice, using c-fos expression as a marker. The study builds upon the established monoaminergic hypothesis of depression and aims to further elucidate the specific brain circuitry involved in antidepressant action. The findings presented in this preprint largely corroborate the existing paradigm by demonstrating a convergence of different antidepressant treatments on a shared limbic-frontal circuit, but with distinct temporal and dose-dependent activation profiles. While suggesting potential refinements to our understanding of antidepressant mechanisms, the study primarily operates within the framework of normal science, seeking to expand and refine existing knowledge rather than challenging or replacing the dominant paradigm. While the described 'core circuit' could be interpreted as a novel model, additional research will be needed to solidify its role. Thus, I am most confident in classifying the preprint as 'Normal Science' with 'Model Drift' being a close alternative classification.