Psilocybin Elicits a Conserved Glucocorticoid-Responsive Gene Signature Across Five 5-HT2A Receptor-Rich Brain Regions in the Male Rat

ABSTRACT: psychedelics are a class of substances best known for their extraordinary mind-altering effects, psychoactive properties that give them both opportunities and risks towards people’s mental health. Based on evidence from clinical trials, psilocybin, a widely used psychedelic for research purposes, appears to produce long-lasting therapeutic effects with minimal physical side effects in patients with a range of mood and addictive disorders. However, as psilocybin profoundly impacts perception, emotion, cognition and the sense of self, it is difficult to use it in the same way that ordinary candidate compounds with therapeutic potential are tested in routine daily clinical trials. Preclinical experiments can therefore provide valuable insights into the molecular mechanisms underlying the reported clinical effectiveness of the compound. Several lines of evidence strongly suggest that psilocybin exerts its effects through 5-HT2A receptors located postsynaptically to serotonergic neurons, particularly concentrated in the frontal cortex, parts of the limbic system (i.e., amygdala and hippocampus), and striatum. In an attempt to improve our knowledge of regional patterns of gene expression in the brain induced by psilocybin, we have generated a global map of gene expression in selected regions of adult rat brain (medial prefrontal cortex, cingulate cortex, hippocampus, and striatum; both right and left sides) using 3prime-RNASeq technology. While our findings revealed a few differentially expressed genes (DEGs) to be present in two or more regions, others had a region-specific profile. Additionally, pathways normally activated by glucocorticoids were found to be enriched in all the examined brain regions following psilocybin treatment.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE284065 | GEO | 2026/04/29

REPOSITORIES: GEO