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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Head-twitch response | 5/5 | https://en.wikipedia.org/wiki/Head-twitch_response | reference | science, encyclopedia | 2026-05-05T07:29:09.145592+00:00 | kb-cron |
The HTR was first described as an effect induced by LSD, independently by Winter and Flataker and by Keller and Umbreit, in 1956. Subsequently, it was described as an effect of large doses of 5-HTP, by Corne, Pickering, and Warner, in 1963. At first, the HTR was just a pharmacological curiosity and was not used as a tool in scientific research. In 1967 however, Corne and Pickering demonstrated the influence of a wide range of drugs on the HTR and proposed the HTR as a behavioral predictor of hallucinogenic effects in humans. The reliability of the HTR for identifying psychedelics is said to have been established by the mid-1970s. However, it has been said that the HTR test did not become widely used in studying serotonin 5-HT2A receptor activation until the mid-2000s. Studies published in the 1960s and 1970s had shown that serotonin receptor antagonists, such as cinanserin, methysergide, and cyproheptadine, blocked the hallucinogen-like effects of psychedelics in animals. Mediation of the HTR specifically via serotonin 5-HT2 receptor agonism was first proposed by Peroutka, Lebovitz, and Snyder in 1981, followed by supporting studies by Ortmann and colleagues in 1982 and Leysen and colleagues also in 1982. Richard Glennon and colleagues further supported mediation of the hallucinogen-like effects of psychedelics by serotonin 5-HT2 receptor agonism with subsequent studies, for instance employing drug discrimination, in 1983 and thereafter. However, the role of the serotonin 5-HT2A receptor in the mediation of psychedelic-like effects, including the HTR, was not conclusively validated until studies with serotonin 5-HT2A receptor knockout mice were published in 2003. It was found in 1985 that the non-hallucinogenic serotonin receptor agonist lisuride did not produce the HTR in animals and could antagonize the HTR induced by other drugs, leading to the suggestion that it was a low-efficacy partial agonist of the serotonin 5-HT2 receptors. Automation of the HTR assay was first described by Adam Halberstadt and colleagues in 2013. They developed a semi-automated assay using magnetometer-based detection. de la Fuente Revenga and colleagues developed a fully automated HTR test based on Halberstadt's work and published their system in 2019. Additional automated HTR systems, including ones employing deep learning techniques, were developed in 2020 and thereafter.
== Other tests == The only other behavioral paradigms for assessment of psychedelic-like effects in animals at present are drug discrimination (DD) and, to a lesser extent, prepulse inhibition (PPI) and time perception. However, the HTR is far less costly and time-consuming than drug discrimination and hence has become much more popular in recent years. Other paradigms for assessing psychedelic-associated effects have also been studied but have not shown satisfactory consistency for general use. In the 2020s, a test of psychedelic-induced visual distortions in animals was published. This study marked the first evidence of psychedelic-induced visual distortions in animals. However, a much earlier test of psychedelic-related visual changes, described by the late 1960s, was a visual object size discrimination task in monkeys.
== See also == Drug discrimination
== References ==
== External links == Psychedelic or Not: Of Mice, 5-HT2A Agonists, and Head Shakes (February 1, 2022) - Nate Seltenrich - Psychedelic Science Review (PSR) Do Mice Hallucinate? Do Humans Head-Twitch? (February 24, 2023) - Psychedelic Alpha LSD & The Head Twitch Response - Hamilton Morris (with Jason Wallach) - YouTube Getting High On HIV Medication (short segment on head-twitch response) - Hamilton Morris - VICE - YouTube The Search for Non-Hallucinogenic Psychedelics: Uncovering the Head Twitch Response - Mind & Matter Podcast Head-twitch response (psilocybin) - Alex Kwan - YouTube