Effects of the N,N-DMT over the diathesis and phenotype of depression in adult mice
neurogenesis; N,N-DMT; depression; plasticity.
Depression is a neurologic disturb that in 2017 afflicted 4.4% of global population, characterized by apathy and anhedonia which affect social and professional life of the ill. The diathesis of depression is not yet satisfactorily understood, however genetic, humoral, environmental and behavioral factors contribute to it in some degree. The classical antidepressants are serotoninergic drugs with slow onset and side effects which are frequently more harmful for the clinical condition than the desired effects. In the last two decades the Neurogenic Hypothesis of Depression points to the generation of new neurons in the adult hippocampus as the neurobiological mechanism sufficient for symptom mitigation by classical antidepressants, in parallel the psychedelics ascend as drugs capable of enhance neuronal plasticity, unfortunately their hallucinogenic potential restrained its assimilation by clinical practice. At this moment of the psychedelic research its necessary to comprehend the contribution of the peak subjective experience, the psychedelic experience, to their therapeutic potential, then we can focus on delineate more effective, affordable and wide application of such compounds to human populations. In this work we intend to induce depression in mice through the Unpredictable Chronic Mild Stress model, and evaluate how a single dose of N,N-Dimethyltryptamine (DMT) affect the symptoms and biomarkers of depression, while we also apply the treatment to anesthetized animals so we can evaluate if the DMT neurotrophic aftermath is dependent of the psychedelic acute experience. To amplify the reach of our experiments, we intend to use the tool DREADD which has genetic precision to exclusively activate newborn granule cells pinned in time, and posteriorly evaluate the effective of those newborn populations in mitigate the symptoms of depression, may it be enhanced by DMT of by DREADD excitation.