Regulation of 5-HT2A receptor mRNA levels and binding sites in rat frontal cortex by the agonist DOI and the antagonist mianserin

A. Anji, M. Kumari, N. R. Sullivan Hanley, G. L. Bryan, J. G. Hensler

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

In the present study we have characterized the time course of effect of administration of the serotonin2 (5-HT2) receptor antagonist mianserin, or the 5-HT2 receptor agonist (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), on 5-HT2A receptor binding sites and mRNA levels in rat frontal cortex. Radioligand binding and ribonuclease protection assays were performed with separate hemispheres of frontal cortex from each animal to examine concomitant changes in 5-HT2A receptor sites and mRNA levels. The decrease in cortical 5-HT2A receptor sites in response to chronic DOI administration was not accompanied by changes in 5-HT2A receptor mRNA. A single injection of DOI produced a transient decrease in 5-HT2A receptor mRNA levels detected 1 h post-injection. The density of 5-HT2A receptor sites, however, was not significantly reduced following a single injection of DOI. The down- regulation of cortical 5-HT2A receptor sites in response to a single injection of mianserin was accompanied by reductions in 5-HT2A receptor mRNA levels. Following 4 days of mianserin administration, however, we did not observe a change in 5-HT2A receptor mRNA levels, although 5-HT2A receptor density was decreased. Thus, changes in receptor mRNA may initially contribute to the down-regulation of 5-HT(2A) receptors in response to acute mianserin administration. Sustained changes in 5-HT2A receptor mRNA, however, appear not to be involved in maintaining the down-regulation of 5- HT2A receptor number with chronic mianserin administration. Mechanisms other than the regulation of receptor mRNA levels appear to underlie the down-regulation of 5-HT2A receptor sites in response to chronic administration of the agonist DOI.

Original languageEnglish (US)
Pages (from-to)1996-2005
Number of pages10
JournalNeuropharmacology
Volume39
Issue number11
DOIs
StatePublished - Oct 2000

Keywords

  • 5-HT(2A) receptor
  • DOI
  • Ketanserin
  • MRNA
  • Mianserin
  • Ribonuclease protection assay

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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