Blocking a specific serotonin receptor stops psilocybin's antidepressant-like effect in rats

Psilocybin produced a rapid and sustained decrease in immobility and an increase in climbing behavior in the forced swim test (FST).

• Psilocybin was administered at a dose of 0.32 mg/kg to Wistar rats.
• Behavioral effects of psilocybin were assessed both on day 1 (rapid) and day 21 (sustained).
• The 5-HT2B receptor antagonist RS-127445, at doses of 0.32, 1.0, or 3.2 mg/kg, blocked the psilocybin-induced behavioral changes in the FST.
• RS-127445 did not affect the head-twitch response, a measure of psychedelic effects.
• The findings suggest that 5-HT2B receptors are necessary for psilocybin's effects on immobility and climbing behavior in the FST.

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