Fluoxetine gradually increases [125I]DOI-labelled 5-HT2A/2C receptors in the hypothalamus without changing the levels of Gq- and G11-proteins.
The time course of fluoxetine-induced supersensitivity of hypothalamic 5-HT2A/2C receptors was examined. Daily injections of fluoxetine (7 or 14 days) significantly increased agonist ([125I]DOI)-labeled high-affinity-state 5-HT2A/2C receptors in the hypothalamus, but not frontal cortex. No change was observed in the density of [3H]ketanscrin-labeled 5-HT2A receptors in either brain region. The levels of Gq- and G11- proteins in the hypothalamus and cortex were not altered by fluoxetine. These results suggest that fluoxetine gradually increases the G-protein coupling of 5-HT2A/2C receptors without altering the levels of Gq- or G11-proteins.
Li
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Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Muma
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NA
Battaglia
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G
Van de Kar
L D
LD
D000662:Amphetamines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015151:Immunoblotting; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000662:Amphetamines; D005473:Fluoxetine; D019204:GTP-Binding Proteins; D007650:Ketanserin; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine