The head-twitch response (HTR) is a rapid side-to-side head movement that occurs in mice and rats after the serotonin 5-HT2A receptor is activated. The prefrontal cortex may be the neuroanatomical locus mediating the HTR. Many serotonergic hallucinogens, including lysergic acid diethylamide (LSD), induce the head-twitch response, and so the HTR is used as a behavioral model of hallucinogen effects. However while there is generally a good correlation between compounds that induce head twitch in mice and compounds that are hallucinogenic in humans, it is unclear whether the head twitch response is primarily caused by 5-HT2A receptors, 5-HT2C receptors or both, but recent evidence shows that the 5-HT2A receptor is solely responsible. Also, the effect can be non-specific, with head twitch responses also produced by some drugs that do not act through 5-HT2 receptors, such as phencyclidine, yohimbine, atropine and cannabinoid receptor antagonists. As well, compounds such as 5-HTP, fenfluramine and 1-Methylpsilocin can also produce head twitch and do stimulate serotonin receptors, but are not hallucinogenic in humans. This means that while the head twitch response can be a useful indicator as to whether a compound is likely to display hallucinogenic activity in humans, the induction of a head twitch response does not necessarily mean that a compound will be hallucinogenic, and caution should be exercised when interpreting such results.
- Nakagawasai, O; Arai, Y; Satoh, SE; Satoh, N; Neda, M; Hozumi, M; Oka, R; Hiraga, H; Tadano, T (January 2004). "Monoamine Oxidase and Head-Twitch Response in Mice Mechanisms of α-Methylated Substrate Derivatives". NeuroToxicology. 25 (1–2): 223–232. PMID 14697897. doi:10.1016/S0161-813X(03)00101-3.
- Willins, DL; Meltzer, HY (August 1997). "Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats.". The Journal of Pharmacology and Experimental Therapeutics. 282 (2): 699–706. PMID 9262333.
- Carbonaro, Theresa M. (July 3, 2014). "The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice". Psychopharmacology. 232 (1): 275–284. PMC . PMID 24985890. doi:10.1007/s00213-014-3658-3.
- Canal, Clint E.; Morgan, Drake (July 2012). "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 Testing and Analysis. 4 (7–8): 556–576. PMC . PMID 22517680. doi:10.1002/dta.1333.