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Head-twitch response
The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin consistently induce the HTR in rodents, whereas non-hallucinogenic serotonin 5-HT2A receptor agonists do not. Because of this, the HTR is widely employed in scientific research as an animal behavioral model of hallucinogen effects and in the discovery of new psychedelic drugs.
The HTR is one of the only behavioral paradigms for assessment of psychedelic-like effects in animals, with the other most notable test being drug discrimination. However, the HTR is far less costly and time-consuming than drug discrimination and hence has become much more popular in recent years. Limitations of the HTR include the fact that various other drugs besides serotonin 5-HT2A receptor agonists, such as NMDA receptor antagonists and muscarinic acetylcholine receptor antagonists, also induce the HTR, and certain indirect non-hallucinogenic serotonin 5-HT2A receptor activators, like 5-hydroxytryptophan (5-HTP) and serotonin releasers, induce the response as well. While a useful test, it should not be regarded as a definitive predictor of human psychedelic potential.
The HTR was first described as an effect of psychedelics in the mid-1950s. It was subsequently proposed as a behavioral test of psychedelic-like effects in 1967. The HTR became widely used as a test of psychedelic-like effects by the mid-2000s. Automated versions of the HTR test, allowing for high-throughput screening, were developed in the 2010s and 2020s.
The HTR is a rapid, rhythmic side-to-side or rotational head movement that intermittently occurs in mice and rats in association with central serotonin 5-HT2A receptor activation. In mice, each individual head movement lasts about 10 milliseconds and each HTR consists of 5 to 11 individual head movements. The HTR is spontaneous and irregularly occurring over the drug's duration. Head twitches also occur naturally in rodents but occur at low frequencies and are only rarely observed in non-stimulated animals. Drugs inducing the HTR cause the frequency to increase by many orders of magnitude above the spontaneous rate. Within a 10-minute period, between 4 and 68 head twitches have been observed following administration of DOI, depending on the dose, enantiomer, and rodent species and strain. The head twitches produced by HTR-inducing drugs are identical to spontaneous head twitches and to touch-induced head twitches (also known as the pinna reflex).
In rats, the HTR is also sometimes known instead as wet dog shakes (WDS). This is because the response in rats can involve more of the whole body instead of just the head shaking and can resemble the shaking of dogs coming out of water. On account of the preceding, the test has also been referred to as the head-twitch response/wet dog shake (HTR/WDS) test.
Serotonin 5-HT2A receptor agonists show an inverted U-shaped dose–response curve for induction of the HTR in terms of its frequency. Tolerance rapidly develops to the induction of the HTR with many but not all serotonergic psychedelics. More specifically, tolerance has been observed with LSD, DOB, DOI, 2C-T-7, 25CN-NBOH, and 5-MeO-AMT, but not with DPT or DiPT. Development of tolerance to the HTR and other serotonin 5-HT2A receptor agonist effects in animals parallels the rapid development of tolerance to the hallucinogenic effects of many psychedelics in humans, including LSD, DOM, psilocybin, and mescaline, among others. Conversely, similarly to the HTR with DPT and DiPT, tolerance does not appear to develop to the psychedelic effects of DMT, ayahuasca (which contains DMT), or 5-MeO-DMT in humans. Time-dependent supersensitivity to the HTR in animals has also been reported, for instance with DOI.
The effective doses (ED50) of numerous serotonergic psychedelics in producing the HTR have been reviewed as well as correlated with human psychedelic doses.
The HTR is also known to occur in rabbits and certain mole-like shrews such as the least shrew. Conversely, it does not occur in other species like primates or humans. However, HTR-like behaviors are also induced by psychedelics in certain other animal species, for instance cats and stump-tailed macaque monkeys. Other related behaviors to head twitches induced by serotonergic agents in animals include ear scratching in mice, limb jerks or flicks in cats, head bobs in rabbits, and body scratches. However, other behaviors induced by psychedelics may not be as reliable as the HTR. In addition, ear scratches appear to be mediated primarily by activation of the serotonin 5-HT2C receptor rather than by activation of the serotonin 5-HT2A receptor. On the other hand, psychedelic-induced head bobs in rabbits appear to be mediated specifically by central serotonin 5-HT2A receptor activation.
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Head-twitch response AI simulator
(@Head-twitch response_simulator)
Head-twitch response
The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin consistently induce the HTR in rodents, whereas non-hallucinogenic serotonin 5-HT2A receptor agonists do not. Because of this, the HTR is widely employed in scientific research as an animal behavioral model of hallucinogen effects and in the discovery of new psychedelic drugs.
The HTR is one of the only behavioral paradigms for assessment of psychedelic-like effects in animals, with the other most notable test being drug discrimination. However, the HTR is far less costly and time-consuming than drug discrimination and hence has become much more popular in recent years. Limitations of the HTR include the fact that various other drugs besides serotonin 5-HT2A receptor agonists, such as NMDA receptor antagonists and muscarinic acetylcholine receptor antagonists, also induce the HTR, and certain indirect non-hallucinogenic serotonin 5-HT2A receptor activators, like 5-hydroxytryptophan (5-HTP) and serotonin releasers, induce the response as well. While a useful test, it should not be regarded as a definitive predictor of human psychedelic potential.
The HTR was first described as an effect of psychedelics in the mid-1950s. It was subsequently proposed as a behavioral test of psychedelic-like effects in 1967. The HTR became widely used as a test of psychedelic-like effects by the mid-2000s. Automated versions of the HTR test, allowing for high-throughput screening, were developed in the 2010s and 2020s.
The HTR is a rapid, rhythmic side-to-side or rotational head movement that intermittently occurs in mice and rats in association with central serotonin 5-HT2A receptor activation. In mice, each individual head movement lasts about 10 milliseconds and each HTR consists of 5 to 11 individual head movements. The HTR is spontaneous and irregularly occurring over the drug's duration. Head twitches also occur naturally in rodents but occur at low frequencies and are only rarely observed in non-stimulated animals. Drugs inducing the HTR cause the frequency to increase by many orders of magnitude above the spontaneous rate. Within a 10-minute period, between 4 and 68 head twitches have been observed following administration of DOI, depending on the dose, enantiomer, and rodent species and strain. The head twitches produced by HTR-inducing drugs are identical to spontaneous head twitches and to touch-induced head twitches (also known as the pinna reflex).
In rats, the HTR is also sometimes known instead as wet dog shakes (WDS). This is because the response in rats can involve more of the whole body instead of just the head shaking and can resemble the shaking of dogs coming out of water. On account of the preceding, the test has also been referred to as the head-twitch response/wet dog shake (HTR/WDS) test.
Serotonin 5-HT2A receptor agonists show an inverted U-shaped dose–response curve for induction of the HTR in terms of its frequency. Tolerance rapidly develops to the induction of the HTR with many but not all serotonergic psychedelics. More specifically, tolerance has been observed with LSD, DOB, DOI, 2C-T-7, 25CN-NBOH, and 5-MeO-AMT, but not with DPT or DiPT. Development of tolerance to the HTR and other serotonin 5-HT2A receptor agonist effects in animals parallels the rapid development of tolerance to the hallucinogenic effects of many psychedelics in humans, including LSD, DOM, psilocybin, and mescaline, among others. Conversely, similarly to the HTR with DPT and DiPT, tolerance does not appear to develop to the psychedelic effects of DMT, ayahuasca (which contains DMT), or 5-MeO-DMT in humans. Time-dependent supersensitivity to the HTR in animals has also been reported, for instance with DOI.
The effective doses (ED50) of numerous serotonergic psychedelics in producing the HTR have been reviewed as well as correlated with human psychedelic doses.
The HTR is also known to occur in rabbits and certain mole-like shrews such as the least shrew. Conversely, it does not occur in other species like primates or humans. However, HTR-like behaviors are also induced by psychedelics in certain other animal species, for instance cats and stump-tailed macaque monkeys. Other related behaviors to head twitches induced by serotonergic agents in animals include ear scratching in mice, limb jerks or flicks in cats, head bobs in rabbits, and body scratches. However, other behaviors induced by psychedelics may not be as reliable as the HTR. In addition, ear scratches appear to be mediated primarily by activation of the serotonin 5-HT2C receptor rather than by activation of the serotonin 5-HT2A receptor. On the other hand, psychedelic-induced head bobs in rabbits appear to be mediated specifically by central serotonin 5-HT2A receptor activation.