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. 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.

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.

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