CHRONIC CITALOPRAM AND FLUOXETINE TREATMENTS UP-REGULATE 5-HT2C RECEPTORS IN THE RAT CHOROID-PLEXUS

The effects of chronic (for 14 clays) citalopram and fluoxetine treatm ents with three doses (2.5, 10, and 20 mg/kg) and withdrawal times (24 hours, 68 hours, and 24 days) on 5-HT2C (formerly 5-HT1C) receptors i n the rat bl ain choroid plexus were studied with quantitative recepto r autoradiography in two separate experiments. Chronic citalopram trea tment 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 ([H-3]mesulergine) than with an agonist ligand (2,5-dimethoxy-4-[I-125]iodophenyl)-2-aminopropane ( [(125)]DOI)]. The uppegulation was most evident 24 hours after the las t dose and disappeared thereafter rather vapidly. Chronic fluoxetine t reatment also increased the density of 5-HT2C receptors 24 hours from the last dose, but the increase tons accompanied by a reduced affinity and was less marked than that observed with citalopram. The changes i n receptor characteristics were not observed consistently after the 68 -hour withdrawal from fluoxetine. Furthermore, the upregulation of flu oxetine appeared not to be dose related or reflected by an increase in agonist binding. In conclusion, the results show that chronic citalop ram and fluoxetine treatments induce an increase of choroid plexus 5-H T2C receptor density, but the effect is more marked with citalopram. T hese differences in the regulation of the 5-HT2C receptors may lead to pharmacodynamic differences between chronic citalopram and fluoxetine treatments.