Do functional relationships exist between 5-HT1A and 5-HT2 receptors?

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.

Study at a glance

Abstract

To investigate the possible functional relationship between 5-HT1 and 5-HT2 receptors, we studied the effects of a nonselective 5-HT agonist (5-MeO DMT), a 5-HT1A-selective (8-OH-DPAT) and a 5-HT1B/5-HT1C-selective (TFMPP) agonist on the head-twitch behavior induced by the putative 5-HT2-selective receptor agonist (+/-)-DOI. In the mouse (+/-)-DOI produced the head-twitch response in a dose-dependent manner and (-)-DOI was twice as potent as the (+) isomer. Selective 5-HT2 antagonists, ketanserin and spiperone, dose-dependently inhibited the (+/-)-DOI-induced head-twitch response. The nonselective and the 5-HT1A-selective agonists also dose-dependently reduced the behavior, whereas 5-HT1B/5-HT1C-selective agonist (TFMPP) failed to affect the (+/-)-DOI-induced response. Taken together with previously published literature data, we propose a 5-HT1A inhibitory action on the 5-HT2 receptor-mediated response when induced by its selective agonist (+/-)-DOI.