Role of endogenous serotonin in psychedelic-like effects of psilocybin in mice
The International Journal of Neuropsychopharmacology May 25, 2025 Ines Erkizia-Santamaría, Nerea Martínez-Álvarez, Leyre Salinas-Novoa et al. 7 citations
The intensity of acute psychedelic effects from psilocybin is inversely related to cortical serotonin levels. In mice, the head-twitch response—a behavioral measure of psychedelic-like effects—was lower in animals lacking the serotonin 2A receptor and was dose-dependently reduced by the antidepressant citalopram, which increases synaptic serotonin. Conversely, depleting serotonin with p-chlorophenylalanine potentiated the response. A serotonin 1A receptor agonist also decreased the response, indicating functional interaction between receptor types. These findings suggest that prior antidepressant treatment may influence individual variability in acute responses to psilocybin, with implications for optimizing psychedelic-based therapies.