Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors.
Daily administration of D-lysergic acid diethylamide (LSD) was previously shown to decrease serotonin2 (5-HT2) receptor binding in rat brain. Recently, 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropane, the substitution being with either iodine (DOI) or bromine (DOB), have been suggested to be relatively selective 5-HT2 agonists. These compounds share common behavioral and neurophysiological effects with LSD, suggested to be 5-HT2 receptor mediated, and the purpose of the present study was to determine whether they also affect 5-HT2 receptor binding after systemic administration in a similar way to LSD. Administration of DOI (1.0 mg/kg) or DOB (0.5 mg/kg) for 7 days resulted in a decrease in 5-HT2 binding, as evaluated with [3H]ketanserin, similar to the decrease after LSD. In a further evaluation of the parallelism of LSD and 5-HT2 agonists, it was found that 24 hr after one administration of a low dose of LSD (130 ug/kg) or DOI (1.0 mg/kg), there was no change in binding, but there was a decrease 24 hr after a high dose (LSD, 650 micrograms/kg; DOI, 7.0 mg/kg). Four hours after the high dose of LSD or DOI there was also a decrease in 5-HT2 binding. Thus, results have shown that 5-HT2 agonists are capable of down-regulating 5-HT2 receptors and that LSD acts in a parallel fashion. This study has also demonstrated that 5-HT2 receptors can be modified within hours after drug administration.
Buckholtz
N S
NS
National Institute of Mental Health, Section on Clinical Pharmacology, Bethesda, MD 20892.
Zhou
D F
DF
Freedman
D X
DX
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006213:Hallucinogens; D007650:Ketanserin / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D000662:Amphetamines; D006213:Hallucinogens; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C003943:2,5-dimethoxy-4-bromoamphetamine; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine