Abstract
N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.
Highlights
N,N-dimethyltryptamine (DMT) is a natural compound found in numerous plant species and botanical preparations, such as the hallucinogenic infusion known as ayahuasca[1] classified as a hallucinogenic compound that induces intense modifications in perception, emotion, and cognition in humans[2,3,4]
We first analyzed whether the sigma-1 receptor (S1R) was expressed on murine neural stem cells (NSC) isolated from the subgranular zone of the dentate gyrus of the hippocampus
We have previously described that β-carbolines alkaloids, the three main alkaloids present in Banisteriopsis caapi and harmol, the main metabolite of harmine in humans, play an important role as key regulators on adult neural stem cell activity[49]
Summary
N,N-dimethyltryptamine (DMT) is a natural compound found in numerous plant species and botanical preparations, such as the hallucinogenic infusion known as ayahuasca[1] classified as a hallucinogenic compound that induces intense modifications in perception, emotion, and cognition in humans[2,3,4]. DMT binds and exerts an agonist activity on subtypes 1A and 2A of the serotonin receptor (5-HT)[17,18] These receptors are Gprotein-coupled receptors (GPCRs) belonging to the family of serotonergic receptors and are involved in numerous cascades of intracellular signaling, with high expression in several regions of the CNS. In mammals, one Morales-Garcia et al Translational Psychiatry (2020)10:331 of the natural endogenous ligands of the σR-1 is DMT14 This receptor has been associated with several cellular functions, including the brain, such as lipid transport, metabolism regulation, cellular differentiation, signaling (in response to stress), cellular protection against oxidant agents, myelination and, most recently, neurogenesis[20,21,22,23,24]
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