Brain region-specific alterations of 5-HT2A and 5-HT2C receptors in serotonin transporter knockout mice

Qian Li, Christine H. Wichems, Li Ma, Louis D. Van de Kar, Francisca Garcia, Dennis L. Murphy

Research output: Contribution to journalArticle

Abstract

The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice.

Original languageEnglish (US)
Pages (from-to)1256-1265
Number of pages10
JournalJournal of Neurochemistry
Volume84
Issue number6
DOIs
StatePublished - Mar 2003
Externally publishedYes

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Keywords

  • 5-HT mRNA
  • 5-HT mRNA, G proteins
  • DOI binding
  • Hormones
  • In situ hybridization

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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