Serotonin 5- HT (2C) 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-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) 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-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) 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-HT(2C) receptors.
López-Giménez
Juan F
JF
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, IIBB-CSIC (IDIBAPS), Barcelona, Spain.
Tecott
Laurence H
LH
Palacios
José M
JM
Mengod
Guadalupe
G
Vilaró
M Teresa
MT
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011869:Radioligand Assay; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics; D014316:Tritium / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000235:genetics*
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014316:Tritium; D012701:Serotonin