The Hallucinogenic Serotonin2A Receptor Agonist, 2,5-Dimethoxy-4-Iodoamphetamine, Promotes cAMP Response Element Binding Protein-Dependent Gene Expression of Specific Plasticity-Associated Genes in the Rodent Neocortex
Frontiers in Molecular Neuroscience December 24, 2021 Lynette A. Desouza, Madhurima Benekareddy, Sashaina E. Fanibunda et al. 46 citations
The hallucinogenic compound DOI, which activates the 5-HT2A receptor, rapidly increases the expression of several genes linked to neuronal plasticity in rat cortical neurons and neocortex. This upregulation involves the transcription factor CREB, which becomes phosphorylated through MAP kinase and CaMKII signaling pathways. DOI enhanced CREB binding to specific gene promoters (Arc, Bdnf1, Cebpb, cFos) but not others (Egr1, Egr2). In mice lacking CREB, DOI-induced expression of Arc, cFos, and Cebpb was significantly reduced. The findings suggest that serotonergic psychedelics may recruit CREB to drive rapid psychoplastogenic effects, similar to slower-acting antidepressants.