In mice, the drug (+/-)-DOI, which activates 5-HT2 receptors, causes a head-twitch response that increases with dose. The (-) isomer of DOI is twice as potent as the (+) isomer. Selective 5-HT2 blockers (ketanserin and spiperone) reduce this response in a dose-dependent way. A nonselective 5-HT agonist (5-MeO DMT) and a 5-HT1A-selective agonist (8-OH-DPAT) also reduce the response, but a 5-HT1B/5-HT1C-selective agonist (TFMPP) does not. The authors propose that 5-HT1A receptors inhibit the 5-HT2 receptor-mediated head-twitch response.
Cocaine acutely suppresses a serotonin-related behavior in mice (the head-twitch response) by activating other receptors, not by blocking 5-HT3 receptors. During withdrawal from chronic cocaine treatment, the same behavior becomes enhanced, indicating supersensitivity that can last up to 172 hours depending on the cocaine dose. Low-dose chronic cocaine withdrawal increases the response to a selective 5-HT2 agonist, while higher doses do not. Withdrawal also increases the inhibitory effect of a 5-HT1A agonist on the behavior.