Psilocybin reduced marble burying in mice, a behavior used to model obsessive-compulsive disorder, but this effect did not depend on the serotonin 2A or serotonin 1A receptors typically associated with psychedelic effects. The 5-HT1A agonist 8-OH-DPAT also reduced marble burying, and its effect was additive with psilocybin, while the 5-HT1A partial agonist buspirone reduced marble burying without adding to psilocybin's effect. Blocking 5-HT1A receptors with WAY100635 did not attenuate psilocybin's effect. A staggered psilocybin regimen over 3.5 hours had no effect, and the effect of a single injection was not persistent. Co-administration of buspirone blocked psilocybin's head twitch response, a rodent correlate of psychedelic effects, suggesting buspirone might block psychedelic effects without impairing anti-obsessional effects.
In mice, psilocybin reduced marble-burying, a behavior linked to obsessive-compulsive disorder, as effectively as the antidepressant escitalopram. This effect was not blocked by a 5-HT2A antagonist or a 5-HT1A antagonist, indicating neither receptor is essential for psilocybin's anti-obsessional action. The 5-HT1A partial agonist buspirone also reduced marble-burying, but combining buspirone with psilocybin did not enhance the effect. Staggered doses of psilocybin over 3.5 hours had no effect, and the effect of a single injection was not persistent. Importantly, buspirone blocked psilocybin's head-twitch response, a rodent correlate of psychedelic effects, suggesting buspirone could prevent psychedelic effects without interfering with anti-obsessional benefits.