A single dose of 5-MeO-DMT stimulates adult neurogenesis in mouse dentate gyrus

Abstract

The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few brain regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5- Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing powerful psychedelic states. Recently, it has been suggested that N,NDimethyltryptamine (DMT) analogues can be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeODMT is capable of increasing DG neurogenesis in vivo. We show that a single intracerebroventricular injection of 5-MeO-DMT increases cell proliferation in the DG, as evinced by 5-Bromo-2′-deoxyuridine (BrdU) staining. Moreover, using a transgenic mouse that expresses tamoxifen-dependent Cre recombinase under doublecortin (DCX) promoter control, we found that newborn DG granule cells have more complex dendritic morphology after 5-MeODMT. Moreover, newborn granule cells display longer afterhyperpolarization potentials (AHP) and lower action potential threshold when compared to 5-MeO-DMT treated. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.