Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors

J Neurosci Res. 2002 Jan 1;67(1):69-85. doi: 10.1002/jnr.10072.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Brain / cytology
  • Brain / metabolism*
  • Brain Chemistry / genetics*
  • Carrier Proteins / metabolism
  • Gene Expression Regulation / genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins*
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA, Messenger / metabolism*
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / deficiency*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism*
  • Serotonin Agents / pharmacokinetics
  • Serotonin Plasma Membrane Transport Proteins
  • Signal Transduction / genetics
  • Synaptic Transmission / genetics
  • Tritium / pharmacokinetics
  • Up-Regulation / genetics*

Substances

  • Carrier Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Tritium
  • Serotonin