5-HYDROXYTRYPTAMINE1C RECEPTOR DENSITY AND MESSENGER-RNA LEVELS IN CHOROID-PLEXUS EPITHELIAL-CELLS AFTER TREATMENT WITH MIANSERIN AND (-)-1-(4-BROMO-2,5-DIMETHOXYPHENYL)-2-AMINOPROPANE

5-Hydroxytryptamine (5HT)1C and 5HT2 receptors display paradoxical dow n-regulation when exposed to receptor antagonists in vivo, a property that is unique to these two subtypes of serotonin (5HT) receptors. Bec ause of the absence of cell culture model systems, the mechanisms invo lved in this paradoxical down-regulation have been difficult to explor e The present study focuses on the regulation of 5HT1C receptors in pr imary cultures of rat choroid plexus epithelial cells. Exposure of the epithelial cell cultures to 100 nm mianserin, a receptor antagonist, or -)-1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane, an agonist, for 72 hr caused a loss of 5HT1C receptor binding sites, as determined by [H-3]mesulergine binding to crude membrane preparations. No significan t changes in K(d) values were observed. Neither the agonist nor antago nist caused a significant change in binding sites after 24 hr. A solut ion hybridization assay was used to determine whether the down-regulat ion by mianserin or (-)-1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane was accompanied by a decrease in the steady state level of 5HT1C rece ptor mRNA. These studies showed that neither treatment caused an alter ation in the levels of 5HT1C receptor mRNA. Thus, it is possible to re produce the in vivo regulatory effects of drugs on 5HT1C receptors in choroid plexus epithelial cells in culture, including the atypical dow n-regulation by receptor antagonists. Using this cell culture model sy stem, indirect transynaptic effects and decreases in receptor mRNA lev els have been ruled out as mechanisms accounting for the down-regulati on.