Naunyn-Schmiedeberg's archives of pharmacology
May 1, 2024
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
31 citations
Serotonergic psychedelics like psilocin (the active metabolite of psilocybin), DOI, and TCB-2 produce antidepressant-like effects in mice by activating the 5-HT2A receptor. Twenty-four hours after a single injection, treated mice showed significantly less immobility in the forced swimming test and tail-suspension test—indicating reduced behavioral despair—compared to control mice. Blocking the 5-HT2A receptor with volinanserin eliminated these antidepressant-like effects. Psilocin's effect in the forced swimming test lasted at least three weeks. In the novelty-suppressed feeding test, psilocin reduced feeding latency (an anxiolytic-like effect), but volinanserin did not block this, and DOI and TCB-2 had no effect. None of the drugs altered spontaneous movement or head-twitch response. The findings suggest 5-HT2A activation mediates antidepressant but not anxiolytic effects of these psychedelics.
Research Square (Research Square)
July 7, 2023
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
4 citations
Serotonergic psychedelics like psilocin, DOI, and TCB-2 produce antidepressant-like effects in mice by activating the serotonin 5-HT2A receptor. Mice given a single injection of these drugs showed less immobility in the forced swimming and tail-suspension tests 24 hours later, effects blocked by a 5-HT2A antagonist. The antidepressant-like effect of psilocin lasted at least three weeks. However, only psilocin reduced anxiety-like behavior in the novelty-suppressed feeding test, and this effect was not blocked by the 5-HT2A antagonist. The drugs did not alter spontaneous movement or head-twitch responses. The findings indicate 5-HT2A mediates antidepressant but not anxiolytic effects of these psychedelics.
Neuropsychopharmacol Rep
September 1, 2026
Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.
In a mouse model of social defeat stress, the serotonin 5-HT2A receptor mediates the ability of psilocin to restore deficits in social behavior. Mice repeatedly subjected to social defeat stress showed reduced social interaction, and treatment with psilocin reversed this impairment. The therapeutic effect of psilocin was blocked by a 5-HT2A receptor antagonist and absent in mice lacking the 5-HT2A receptor, indicating that this receptor is necessary for the prosocial action of psilocin. These findings suggest that the 5-HT2A receptor is a key target for psilocin's effects on social behavior deficits caused by chronic stress.