Effects of repeated treatment with fluoxetine and citalopram, 5-HT uptake inhibitors, on 5-HT1A and 5-HT2 receptors in the rat brain.
Repeated treatment with fluoxetine and citalopram, which are potent 5-HT reuptake inhibitors, resulted in different regulation of 5-HT1A and 5-HT2 receptors in the rat brain. Their effects were compared with those of other antidepressants: imipramine, mianserin and levoprotiline. The density of 5-HT1A receptors, labelled with [3H]8-OH-DPAT, in the rat hippocampus was enhanced after citalopram, imipramine, mianserin and levoprotiline, but not altered after fluoxetine administration. [3H]Ketanserin binding sites, which label 5-HT2 receptors, were increased after fluoxetine and levoprotiline, but decreased after citalopram, imipramine and mianserin in the rat cerebral cortex. Acute administration of fluoxetine, but not citalopram, resulted in a decreased density of 5-HT1A receptors. 5-HT2 receptors were not changed by acute administration of either fluoxetine or citalopram. The obtained results indicate that besides 5-HT reuptake inhibiting properties of both compounds, there may exist an additional mechanism(s) of their action, which leads to different regulation of 5-HT1A and 5-HT2 receptors.
Klimek
V
V
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Zak-Knapik
J
J
Mackowiak
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D005473:Fluoxetine; D015283:Citalopram; D008376:Maprotiline; D012701:Serotonin; C027299:hydroxymaprotilin; D007650:Ketanserin