Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 10 No. 5 August 10, 2023 p.189-197
Original Article
An application of the magnetometer detection system to Crl:CD1 (ICR) mice for head twitch response induced by hallucinogenic 5-HT2A agonists
  • Motoki Hojo (Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health /
Mari Nakamura 1) , Motoki Hojo 1) , Ayaka Kawai 1) , Kiyomi Ikushima 1) , Akemichi Nagasawa 1) , Hideyo Takahashi 2) , Kosho Makino 3) , Toshinari Suzuki 1) , Jin Suzuki 1) , Akiko Inomata 1)
1) Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health , 2) Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science , 3) Research Institute of Pharmaceutical Sciences, Musashino University
Keywords: DOI, Hallucinogen, Head twitch response, ICR mice, LSD, Magnetometer

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.