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{{Short description|Head movement in rodants upon 5-HT2A receptor activation}}
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.<ref>{{cite journal |last1=Nakagawasai |first1=O |last2=Arai |first2=Y |last3=Satoh |first3=SE |last4=Satoh |first4=N |last5=Neda |first5=M |last6=Hozumi |first6=M |last7=Oka|first7=R|last8=Hiraga|first8=H|last9=Tadano|first9=T|title=Monoamine Oxidase and Head-Twitch Response in Mice Mechanisms of α-Methylated Substrate Derivatives|journal=NeuroToxicology|date=January 2004|volume=25|issue=1–2|pages=223–232|doi=10.1016/S0161-813X(03)00101-3|pmid=14697897}}</ref> The [[prefrontal cortex]] may be the neuroanatomical locus mediating the HTR.<ref>{{cite journal |last1=Willins |first1=DL |last2=Meltzer|first2=HY|title=Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats.|journal=The Journal of Pharmacology and Experimental Therapeutics|date=August 1997|volume=282|issue=2|pages=699–706|pmid=9262333}}</ref> 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 receptor]]s, [[5-HT2C receptor]]s or both, but recent evidence shows that the HTR is mediated by the 5-HT2A receptor and modulated by the 5-HT2C receptor.<ref>{{cite journal | pmid = 12083749 | doi=10.1254/jjp.89.89 | volume=89 | title=Modulation by 5-hT2A receptors of aggressive behavior in isolated mice | year=2002 | journal=Jpn J Pharmacol | pages=89–92 | last1 = Sakaue | first1 = M | last2 = Ago | first2 = Y | last3 = Sowa | first3 = C | last4 = Sakamoto | first4 = Y | last5 = Nishihara | first5 = B | last6 = Koyama | first6 = Y | last7 = Baba | first7 = A | last8 = Matsuda | first8 = T| doi-access = free }}</ref><ref>{{cite journal|last1=Carbonaro|first1=Theresa M.|title=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|date=July 3, 2014|volume=232|issue=1|pages=275–284|doi=10.1007/s00213-014-3658-3|journal=Psychopharmacology|pmid=24985890|pmc=4282596}}</ref> Also, the effect can be non-specific, with head twitch responses also produced by some drugs that do not act through 5-HT<sub>2</sub> receptors, such as [[phencyclidine]], [[yohimbine]], [[atropine]] and [[cannabinoid receptor antagonist]]s. 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.<ref>{{cite journal|last1=Canal|first1=Clint E.|last2=Morgan|first2=Drake|title=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|journal=Drug Testing and Analysis|date=July 2012|volume=4|issue=7–8|pages=556–576|doi=10.1002/dta.1333|pmid=22517680|pmc=3722587}}</ref>
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.<ref>{{cite journal | vauthors = Nakagawasai O, Arai Y, Satoh SE, Satoh N, Neda M, Hozumi M, Oka R, Hiraga H, Tadano T | display-authors = 6 | title = Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives | journal = Neurotoxicology | volume = 25 | issue = 1–2 | pages = 223–32 | date = January 2004 | pmid = 14697897 | doi = 10.1016/S0161-813X(03)00101-3 | bibcode = 2004NeuTx..25..223N }}</ref> The [[prefrontal cortex]] may be the neuroanatomical locus mediating the HTR.<ref>{{cite journal | vauthors = Willins DL, Meltzer HY | title = Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 282 | issue = 2 | pages = 699–706 | date = August 1997 | pmid = 9262333 }}</ref> 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,<ref name="pmid31917152">{{cite journal | vauthors = Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD | title = Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species | journal = Neuropharmacology | volume = 167 | issue = | pages = 107933 | date = May 2020 | pmid = 31917152 | doi = 10.1016/j.neuropharm.2019.107933 | pmc = 9191653 }}</ref> it is unclear whether the head twitch response is primarily caused by [[5-HT2A receptor]]s, [[5-HT2C receptor]]s or both, though recent evidence shows that the HTR is mediated by the 5-HT2A receptor and modulated by the 5-HT2C receptor.<ref>{{cite journal | vauthors = Sakaue M, Ago Y, Sowa C, Sakamoto Y, Nishihara B, Koyama Y, Baba A, Matsuda T | display-authors = 6 | title = Modulation by 5-hT2A receptors of aggressive behavior in isolated mice | journal = Japanese Journal of Pharmacology | volume = 89 | issue = 1 | pages = 89–92 | date = May 2002 | pmid = 12083749 | doi = 10.1254/jjp.89.89 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB | title = 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 | journal = Psychopharmacology | volume = 232 | issue = 1 | pages = 275–84 | date = January 2015 | pmid = 24985890 | pmc = 4282596 | doi = 10.1007/s00213-014-3658-3 }}</ref> Also, the effect can be non-specific, with head twitch responses also produced by some drugs that do not act through 5-HT<sub>2</sub> receptors, such as [[phencyclidine]], [[yohimbine]], [[atropine]] and [[cannabinoid receptor antagonist]]s. As well, compounds such as [[5-HTP]], [[fenfluramine]], [[1-Methylpsilocin]], [[Ergometrine]], and [[3,4-Dimethoxyphenethylamine|3,4-di-methoxyphenethylamine (DMPEA)]] can also produce head twitch and do stimulate serotonin receptors, but are not hallucinogenic in humans.<ref>{{Cite journal |last1=Corne |first1=S. J. |last2=Pickering |first2=R. W. |date=1967 |title=A possible correlation between drug-induced hallucinations in man and a behavioural response in mice |url=http://link.springer.com/10.1007/BF00401509 |journal=Psychopharmacologia |language=en |volume=11 |issue=1 |pages=65–78 |doi=10.1007/BF00401509 |pmid=5302272 |s2cid=3148623 |issn=0033-3158}}</ref><ref>{{Cite book |last1=Shulgin |first1=Alexander |title=PiHKAL: A Chemical Love Story |last2=Shulgin |first2=Ann |publisher=Transform Press |year=1991 |isbn=978-0-9630096-0-9 |edition=1st |pages=614–616 |language=en}}</ref> 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.<ref>{{cite journal | vauthors = Canal CE, Morgan D | title = 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 | journal = Drug Testing and Analysis | volume = 4 | issue = 7–8 | pages = 556–76 | date = July 2012 | pmid = 22517680 | pmc = 3722587 | doi = 10.1002/dta.1333 }}</ref>
[[File:Head_Twitch_Response_from_different_drugs.png|center|thumb|560x560px|Table of Different HTR inducing drugs]]


==References==
== References ==
{{reflist}}
{{reflist}}



Latest revision as of 00:14, 14 August 2024

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

References

[edit]
  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.