Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia
Neuropsychopharmacology July 18, 2026 James J Gattuso, Ahmed Kamal, Jennyfer M. Payet et al.
In a mouse model of schizophrenia lacking the metabotropic glutamate receptor 5 (mGlu5), psilocybin (1 mg/kg) caused hyperlocomotion, while normal mice showed no such effect. Male knockout mice also had a stronger head-twitch response, indicating enhanced serotonin 2A receptor signaling. Psilocybin increased neural activity in the claustrum of normal but not knockout mice, showing that intact mGlu5 signaling is needed for this effect. Psilocybin did not change anxiety-like behavior but increased immobility in a stress test. Notably, it produced a sustained normalization of sensorimotor gating in female knockout mice nine days after treatment, suggesting sex-dependent long-term effects.