Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model.
Drug Test Anal April 19, 2012
The head-twitch response (HTR) in rodents is a behavioral model widely used to study hallucinogens like 2,5-dimethoxy-4-iodoamphetamine (DOI). This paper provides a comprehensive history of the HTR, re-evaluates its underlying mechanisms, and discusses its utility as a preclinical model for hallucinogen effects. The authors argue that the HTR is mediated primarily by serotonin 5-HT2A receptor activation, though other receptors may modulate it. They conclude that while the HTR is a valuable tool for screening hallucinogenic potential and studying receptor pharmacology, its translational relevance to human psychedelic experiences has limitations. The review synthesizes decades of research to clarify the model's strengths and weaknesses.