Head-twitch response

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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.[1] The prefrontal cortex may be the neuroanatomical locus mediating the HTR.[2] Many serotonergic hallucinogens, including lysergic acid diethylamide (LSD), induce the head-twitch response, 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. Also this 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 as compounds such as 5-HTP, fenfluramine and 1-Methylpsilocin which 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.[3]


  1. ^ Nakagawasai O, Arai Y, Satoh SE, et al. Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives. Neurotoxicology. 2004;25(1-2):223-32.
  2. ^ Willins DL, Meltzer HY. Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats. J Pharmacol Exp Ther. 1997;282(2):699-706.
  3. ^ Canal CE, Morgan D. 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. 2012 Jul-Aug;4(7-8):556-76. DOI 10.1002/dta.1333 PMID 22517680