An application of the magnetometer detection system to Crl:CD1 (ICR) mice for head twitch response induced by hallucinogenic 5-HT_2A agonists

Abstract

The head twitch response (HTR), a rapid reciprocal head movement, is a reliable behavioral indicator in rodents following the administration of hallucinogens. It is considered a model for predicting psychedelic activity in humans. A recently developed magnetometer system, consisting of a head-mounted magnet and a magnetometer coil, offers a promising alternative to laborious manual counting of HTR in animal experiments; however, it requires relatively complex analytical processes. In this study, our aim was to explore a simple and practical application of this system in ICR mice. Mice implanted with magnets were administered lysergic acid diethylamide (LSD) or (±)-2,5-dimethoxy-4-iodoamphetamine (DOI), and their HTRs were recorded using the magnetometer system. The outputted wave signals were subjected to a 2-step screening: cutoffs for frequency band and amplitude, and manual sorting of the resulting waves. Validation through video scoring revealed a high detection accuracy of the magnetometer system, reaching nearly 99%. Next, we conducted detailed dose-response analyses for the two psychedelics at a dose range of 0.01–3 mg/kg (LSD) or 0.1–25 mg/kg (DOI). The dose-response curves displayed typical inverted U-shaped patterns, and the ED₅₀ value was calculated as 0.086 mg/kg for LSD and 1.42 mg/kg for DOI. Lastly, we explored a simpler screening method using a relatively strict set of filtering criteria instead of the 2-step screening process. A series of validation tests demonstrated that this method can detect HTR with a mean error rate of 11.20%. Our findings provide an option for the application of the magnetometer system and offer fundamental information about experimental conditions suitable for conducting HTR tests in ICR mice.