Head-twitch response

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, 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,[3] it is unclear whether the head twitch response is primarily caused by 5-HT2A receptors, 5-HT2C receptors or both, though recent evidence shows that the HTR is mediated by the 5-HT2A receptor and modulated by the 5-HT2C receptor.[4][5] 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, 1-Methylpsilocin, Ergometrine, and 3,4-di-methoxyphenethylamine (DMPEA) can also produce head twitch and do stimulate serotonin receptors, but are not hallucinogenic in humans.[6][7] 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.[8]

Table of Different HTR inducing drugs
  1. ^ Nakagawasai O, Arai Y, Satoh SE, Satoh N, Neda M, Hozumi M, et al. (January 2004). "Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives". Neurotoxicology. 25 (1–2): 223–32. Bibcode:2004NeuTx..25..223N. doi:10.1016/S0161-813X(03)00101-3. PMID 14697897.
  2. ^ 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.
  3. ^ Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology. 167: 107933. doi:10.1016/j.neuropharm.2019.107933. PMC 9191653. PMID 31917152.
  4. ^ Sakaue M, Ago Y, Sowa C, Sakamoto Y, Nishihara B, Koyama Y, et al. (May 2002). "Modulation by 5-hT2A receptors of aggressive behavior in isolated mice". Japanese Journal of Pharmacology. 89 (1): 89–92. doi:10.1254/jjp.89.89. PMID 12083749.
  5. ^ Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB (January 2015). "The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice". Psychopharmacology. 232 (1): 275–84. doi:10.1007/s00213-014-3658-3. PMC 4282596. PMID 24985890.
  6. ^ Corne, S. J.; Pickering, R. W. (1967). "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia. 11 (1): 65–78. doi:10.1007/BF00401509. ISSN 0033-3158. PMID 5302272. S2CID 3148623.
  7. ^ Shulgin, Alexander; Shulgin, Ann (1991). PiHKAL: A Chemical Love Story (1st ed.). Transform Press. pp. 614–616. ISBN 978-0-9630096-0-9.
  8. ^ Canal CE, Morgan D (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): 556–76. doi:10.1002/dta.1333. PMC 3722587. PMID 22517680.