The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen
Psychopharmacology February 19, 2010 Clinton E. Canal, U. B. Olaghere da Silva, P. Gresch et al. 111 citations
The hallucinogenic compound DOI triggers a head-twitch response in mice, which is considered a behavioral proxy for hallucinogenic effects in humans. This response depends on the 5-HT2A serotonin receptor, but the study shows it is also strongly modulated by the 5-HT2C receptor. Mice lacking the 5-HT2C receptor showed about 50% fewer head twitches after DOI administration. Blocking the 5-HT2C receptor with specific antagonists reduced the head-twitch response by at least half in two different mouse strains. Differences in the 5-HT2A receptor did not explain strain variations in the response, suggesting 5-HT2C receptor signaling or other modulators are involved. The finding calls for a reassessment of how hallucinogens work through serotonin receptors.