A simple, noninvasive method using computer analysis of video recordings accurately measures the head twitch response (HTR) in mice, a behavioral proxy for psychedelic drug effects in humans. Male mice injected with the 5-HT2 receptor agonist DOI showed dose-related increases in HTRs (0.03–3 mg/kg), which were blocked by the 5-HT2A antagonist M100907. Computer scoring closely matched visual scoring by trained observers, captured nearly all HTRs, and produced few false positives from behaviors like grooming. Optimizing lighting improved results. This method offers a reliable, surgery-free alternative for studying psychedelic-like activity.
The head twitch response (HTR) in mice is a behavior increased by serotonergic psychedelics and used as a proxy for psychedelic-like effects. This study compared HTRs induced by DOI, LSD, and psilocybin in male and female C57BL/6J mice. Drug potencies for inducing HTRs were similar between sexes for all drugs, with LSD showing increased maximal counts in females. The maximum number of HTRs was higher in females for all drugs, with significant sex differences for DOI and LSD. Dose-by-sex interactions were significant for psilocybin and LSD, with females displaying more HTRs at the highest doses. Locomotor and temperature effects were similar between sexes. Overall, no substantial sex differences in potency were found, but females uniformly showed more HTRs at high doses.