Serotonin 5-HT2C receptor knockout mice: Autoradiographic analysis of multiple serotonin receptors

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT2C receptor knockout mice. The radioligands employed were [3H]citalopram, [3H]WAY100,635, [3H]8-OH-DPAT, [3H]GR125743, [3H]sumatriptan, [3H]MDL100,907, [125I](=)DOI, [3H]mesulergine, [3H]5-HT, [3H]GR113808, and [3H]5-CT. As expected, radioligands that label 5-HT2C receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT2C receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT2A receptor and serotonin transporter mRNA levels, whereas 5-HT2C receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT2C receptors. © 2002 Wiley-liss, Inc.This work was supported by CICYT grant SAF96-0336 to G.M. J.F.L.-G. is a recipient fellowship >Beca de Formació de Personal Investigador Institut d'Investigacions Biomèdiques August Pi i Sunyer.>Peer Reviewe