Mice lacking the serotonin transporter do not respond to the behavioural effects of psilocybin.
European journal of pharmacology March 15, 2025 James J Gattuso, Carey Wilson, Shanshan Li et al. 16 citations
Psilocybin, a serotonergic psychedelic, shows therapeutic potential for depression and anxiety disorders. In a study using serotonin transporter knockout mice—a model for anxiety and depression—a single dose of psilocybin (1 mg/kg) failed to produce head-twitch or hyperlocomotor responses in knockout animals, unlike wild-type mice. Psilocybin did not alter anxiety- or depressive-like behaviors in either genotype, though a trend toward reduced immobility in the Porsolt swim test appeared in female wild-type mice. Female knockout mice uniquely showed anhedonia-like behavior. The findings indicate that functional serotonin transporters are necessary for psilocybin's acute behavioral effects, with implications for pharmacogenetics in humans.