Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout mouse model of compulsive behaviour

Wilson, Carey; Gattuso, James J.; Kuznetsova, Maria; Li, Shanshan; Connell, Sasha; Choo, Jocelyn M.; Rogers, Geraint B.; Gubert, Carolina; Hannan, Anthony J.; Renoir, Thibault

doi:10.1016/j.jad.2024.07.143

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Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour

Gattuso,

Wilson,

Hannan

et al. 2025

Neuropharmacology

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Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour

Gattuso,

Wilson,

Hannan

et al. 2025

Neuropharmacology

View full text Add to dashboard Cite

Psilocybin Reduces Grooming in the SAPAP3 Knockout Mouse Model of Compulsive Behaviour

Gattuso,

Wilson,

Hannan

et al. 2024

Preprint

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Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment. In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1-, 3- and 8-days post-injection). While psilocybin did not have any effect on anxiety-like behaviours, we revealed for the first time that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female WT and SAPAP3 KO mice. We also found that psilocybin increased locomotion in wild-type littermates but not in SAPAP3 KO mice, suggesting in vivo serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes. Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.

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Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout mouse model of compulsive behaviour

Cited by 2 publications

References 39 publications

Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour

Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour

Psilocybin Reduces Grooming in the SAPAP3 Knockout Mouse Model of Compulsive Behaviour

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