Rapid desensitization and down-regulation of 5-HT2 receptors by DOM treatment.

The regulation of the 5-HT2 receptor-mediated head twitch response and of 5-HT2 receptor binding in the frontal cortex was studied in rats treated repeatedly with the 5-HT2 agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) (2.5 mg/kg, s.c.). Four injections in 24 h produced a near maximal reduction in the behaviour (-70%) and in the Bmax for [3H]ketanserin binding (-41%). The KD values tended to increase slightly. 5-HT2 receptors reappeared, with half-lives of 5.5 to 3 days. In view of the reported anomalous 5-HT2 receptor regulation by antagonists and the regular regulation by agonists, we propose a refinement in the receptor regulation theory.