Evaluation of the head twitch response in male C57BL/6J mice as a measure of 5-HT2a receptor activation

SPS 2023 -- The head twitch response (HTR) is a rhythmic paroxysmal rotational head movement that occurs in mice in response to serotonergic hallucinogens and serotonin (5-HT2A) receptor activation. The HTR test is a widely used animal behavioral assay for 5-HT2A receptor activation and to probe for interactions between the 5-HT2A receptor and other transmitter systems. Antipsychotics including the dopamine D2 antagonist haloperidol (typical) and the 5-HT2A antagonist clozapine (atypical), are known to decrease the HTR in mice and hallucinations in humans. The HTR test is, therefore, a useful test for screening novel drugs for the treatment of brain disorders, including schizophrenia. In addition, the HTR is a useful model to evaluate the potential for novel drugs to activate the 5-HT2A receptor or produce a synergistic effect when co-administered with medications known to elevate serotonin levels. The objective of this study was to characterize and validate the HTR in male C57BL/6J mice. Phase I characterized the HTR in C57BL/6J mice by inducing the HTR with various drugs known to activate 5-HT2A receptors and observing the response continuously over a 60-minute period to determine onset, peak and duration of effect. Phase II assessed the potential for the HTR to be attenuated following administration of the antipsychotic drugs haloperidol and clozapine.