Chronic treatment with (+/-)DOI, a psychotomimetic 5-HT2 agonist, downregulates 5-HT2 receptors in rat brain.
(+/-)DOI (2,5-dimethoxy-4-iodo-phenylisopropylamine) is a hallucinogenic phenylalkylamine that has been characterized as a 5-HT2-selective agonist. Chronic treatment with (+/-)DOI [1.0 mg/kg/day (2.8 mumol/kg) for 8 days] significantly reduced the binding of [3H]ketanserin, [125I]LSD, and [125I]R-DOI as measured at single ligand concentrations in rat cortical homogenates. In saturation studies, chronic DOI treatment significantly lowered the Bmax of [3H]ketanserin binding and the high-affinity binding of [125I]R-DOI without altering the Kd values. In rats treated acutely with a single dose of (+/-)DOI, binding of [125I]R-DOI, [125I]LSD, and [3H]ketanserin was not significantly different from controls in membranes preincubated at 37 degrees C for 60 minutes. In all experiments nonspecific binding was determined by incubation with 1 microM ritanserin. This work demonstrates that chronic treatment with a 5-HT2-selective agonist hallucinogen reduces the number of binding sites for 5-HT2 agonists as well as for 5-HT2 antagonists.
McKenna
D J
DJ
Laboratory of Clinical Science, NIMH, Bethesda, MD 20892.
Nazarali
A J
AJ
Himeno
A
A
Saavedra
J M
JM
D000662:Amphetamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*
D000662:Amphetamines; D011985:Receptors, Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine