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.
Leysen
J E
JE
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Janssen
P F
PF
Niemegeers
C J
CJ
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D007279:Injections, Subcutaneous; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*
D000662:Amphetamines; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D007650:Ketanserin