Psilocybin and the serotonin precursor 5-HTP produce a characteristic head twitch response in mice, which is linked to the human psychedelic experience. This response depends primarily on the 5-HT2A receptor, as blocking it with M100907 reduced twitching. Activating the 5-HT1A receptor with 8-OH-DPAT also suppressed the response, while blocking the 5-HT2C receptor with RS-102221 had a bimodal effect—enhancing twitching at lower doses but reducing it at higher doses. Blocking the trace amine-associated receptor 1 (TAAR1) with EPPTB reduced 5-HTP-induced twitching but not psilocybin-induced twitching. These findings highlight multiple receptor systems that could modulate psychedelic effects and may inform therapeutic applications.
Psilocybin and the serotonin precursor 5-HTP both cause a characteristic head twitch response in mice, a behavior linked to the human psychedelic experience. The head twitch response depends primarily on the 5-HT2A receptor, as blocking this receptor with volanserin reduced the response. Activating the 5-HT1A receptor also reduced head twitching. In contrast, blocking the 5-HT2C receptor had a bimodal effect, enhancing the response at lower doses but reducing it at higher doses. Blocking the trace amine associated receptor 1 (TAAR1) reduced head twitching caused by 5-HTP but not by psilocybin, indicating a differential role for this receptor. These findings identify multiple receptors that could be targeted to modulate the effects of psychedelic compounds in therapeutic settings.