Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice
International Journal of Molecular Sciences December 4, 2022 Mireia Medrano, An Buckinx, Ilse Smolders et al. 11 citations
Serotoninergic psychedelics like psilocybin can produce lasting reductions in depressive symptoms, but their mechanism is unclear. In a mouse forced swim test model, the psychedelic DOI was tested for effects on behavior and 5-HT2A receptor levels in the medial prefrontal cortex. Mice exposed to swim stress developed passive coping behavior six days later, but this was not linked to increased head twitch responses or consistent changes in 5-HT2A receptor levels. A low dose of DOI (0.2 mg/kg) unexpectedly increased immobility, while a high dose (2 mg/kg) had no significant effect. DOI did cause a dose-dependent decrease in 5-HT2A levels in stressed mice. These results do not support the idea that downregulating 5-HT2A receptors in the medial prefrontal cortex underlies antidepressant-like effects of serotoninergic psychedelics.