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-HT_2A receptor activation.^[1][2] Serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin consistently induce the HTR in rodents.^[1][3] 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.^[1][3]

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.^[4][5][6][7] However, the HTR is far less costly and time-consuming than drug discrimination and hence has become much more popular in recent years.^[8] Limitations of the HTR include the fact that various other drugs besides serotonin 5-HT_2A receptor agonists, such as NMDA receptor antagonists and muscarinic acetylcholine receptor antagonists, also induce the HTR, and certain indirect non-hallucinogenic serotonin 5-HT_2A receptor activators, like 5-hydroxytryptophan (5-HTP) and serotonin releasers, induce the response as well.^[1][9][8]

The HTR was first described as an effect of psychedelics in the mid-1950s.^{[1][10][5][7]} It was subsequently proposed as a behavioral test of psychedelic-like effects in 1967.^[6][5][11] The HTR became widely used as a test of psychedelic-like effects by the mid-2000s.^[12] Automated versions of the HTR test, allowing for high-throughput screening, were developed in the 2010s and 2020s.^{[13][14][12][15]}