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 radio-ligands employed were [H-3]citalopram, [H-3]WAY100,635, [H-3]8-OH-DPAT, [H-3]GR125743, [H-3]sumatriptan, [H-3]MDL100,907, [I-125](+/-) DOI, [H-3]mesulergine, [H-3]5-HT, [H-3]GR113808, and [H-3]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. (C) 2002 Wiley-Liss, Inc.