Chronic citalopram and fluoxetine treatments upregulate 5-HT2c receptors in the rat choroid plexus.
The effects of chronic (for 14 days) citalopram and fluoxetine treatments with three doses (2.5, 10, and 20 mg/kg) and withdrawal times (24 hours, 68 hours, and 14 days) on 5-HT2C (formerly 5-HT1C) receptors in the rat brain choroid plexus were studied with quantitative receptor autoradiography in two separate experiments. Chronic citalopram treatment caused a consistent and dose-related increase in the density of 5-HT2C receptors (up to 90%). This effect was slightly more pronounced when measured with an antagonist ligand ([3H]mesulergine) than with an agonist ligand [(+/-)-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane ([125I]DOI)]. The upregulation was most evident 24 hours after the last dose and disappeared thereafter rather rapidly. Chronic fluoxetine treatment also increased the density of 5-HT2C receptors 24 hours from the last dose, but the increase was accompanied by a reduced affinity and was less marked than that observed with citalopram. The changes in receptor characteristics were not observed consistently after the 68-hour withdrawal from fluoxetine. Furthermore, the upregulation of fluoxetine appeared not to be dose related or reflected by an increase in agonist binding. In conclusion, the results show that chronic citalopram and fluoxetine treatments induce an increase of choroid plexus 5-HT2C receptor density, but the effect is more marked with citalopram. These differences in the regulation of the 5-HT2C receptors may lead to pharmacodynamic differences between chronic citalopram and fluoxetine treatments.
Laakso
A
A
Department of Pharmacology, University of Turku, Finland.
Pälvimäki
E P
EP
Kuoppamäki
M
M
Syvälahti
E
E
Hietala
J
J
D000662:Amphetamines; D000818:Animals; D000978:Antiparkinson Agents / Q000493:pharmacokinetics; D001345:Autoradiography; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D004873:Ergolines / Q000493:pharmacokinetics; D005473:Fluoxetine / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects*; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000662:Amphetamines; D000978:Antiparkinson Agents; D015283:Citalopram; D004873:Ergolines; D005473:Fluoxetine; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C031649:mesulergine