Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice
Journal of Psychopharmacology – April 28, 2024
Source: OpenAlex
Summary
A single dose of psilocybin rapidly and lastingly alleviated behavioural despair in mice, a compelling finding for neuroscience and psychology. This pharmacology research, relevant to psychedelics and drug studies, reveals psilocybin promotes neuroplasticity in the hippocampus and prefrontal cortex. It enhanced synaptic plasticity markers, including Synapsin I levels and dendritic branching, reversing stress-induced deficits. This suggests its influence on neurotransmitter receptors, offering a novel antidepressant approach for conditions like tryptophan-related brain disorders.
Abstract
Background: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. Aims: To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. Methods: We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. Results: We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). Conclusions: Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.