Drugs

Psilocybin (received from Usona Institute and NIDA Investigational Drug and Material Supply Program) and DOI (Sigma-Aldrich, cat #D101) were dissolved in saline to a concentration of 1 mg/ml. Ketanserin (Sigma-Aldrich, cat #S006) and SB242084 (Tocris, cat #2901) were dissolved in 10% DMSO to a concentration of 1 mg/ml. Solutions were prepared on the day of injection when possible and otherwise stored at −20°C for up to a month. All injections were intraperitoneal. The dosage of 1 mg/kg for psilocybin and DOI has been shown to reliably elicit the head-twitch response, a behavioral marker of psychedelic activity [^22,25]. The chosen dose of ketanserin abolishes the head-twitch responses produced by psilocybin [²²]. We selected a relatively high dose of SB242084, which has behavioral effects in decision-making tasks [^26,27]. Saline, DOI or psilocybin were injected 20 min before behavioral testing. Antagonist were injected 10 min before the main treatment (30 min prior to testing). Animals received multiple injections (min 1, max 4) given at least 2 weeks of washout between injections. Treatments were not repeated in the same animals and given in random order (Supplementary Table S1).