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Research ArticleArticle

A Rapid New Assay to Detect RNA Editing Reveals Antipsychotic-Induced Changes in Serotonin-2C Transcripts

Monsheel S. K. Sodhi, David C. Airey, Warren Lambert, Philip W. J. Burnet, Paul J. Harrison and Elaine Sanders-Bush
Molecular Pharmacology September 2005, 68 (3) 711-719; DOI: https://doi.org/10.1124/mol.105.014134
Monsheel S. K. Sodhi
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David C. Airey
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Warren Lambert
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Philip W. J. Burnet
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Paul J. Harrison
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Elaine Sanders-Bush
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Abstract

We report the development of a new assay as an alternative to direct DNA sequencing to measure RNA-edited variation in tissue. The new assay has been validated and is accurate, cheaper, more rapid, and less labor-intensive than DNA sequencing. We also outline the statistical modeling required for analyses of the hierarchical, clustered RNA-editing data generated in these studies. Using the new technique, we analyzed the effects of long-term antipsychotic medication on serotonin-2C receptor (5-HT2CR) RNA editing in rat brain. Our hypothesis that a drug with high affinity for 5-HT2CR, such as clozapine, would alter its RNA-editing profile was not confirmed. Whereas haloperidol, a typical antipsychotic drug that is primarily a dopamine receptor antagonist, reduced 5-HT2C VNV isoform frequency and the level of RNA editing at the D site, risperidone and not the prototype atypical antipsychotic drug clozapine increased the frequency of 5-HT2C VNV and D-site editing. Our data emphasize that caution is required in the interpretation of RNA-editing data in studies of psychiatric disorders, because these studies usually include subjects who received long-term exposure to medication. This newly established method will facilitate high-throughput investigations of RNA editing in disease pathology and in the pharmacological activity of drugs.

  • Received April 26, 2005.
  • Accepted May 24, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 68 (3)
Molecular Pharmacology
Vol. 68, Issue 3
1 Sep 2005
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Research ArticleArticle

A Rapid New Assay to Detect RNA Editing Reveals Antipsychotic-Induced Changes in Serotonin-2C Transcripts

Monsheel S. K. Sodhi, David C. Airey, Warren Lambert, Philip W. J. Burnet, Paul J. Harrison and Elaine Sanders-Bush
Molecular Pharmacology September 1, 2005, 68 (3) 711-719; DOI: https://doi.org/10.1124/mol.105.014134

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Research ArticleArticle

A Rapid New Assay to Detect RNA Editing Reveals Antipsychotic-Induced Changes in Serotonin-2C Transcripts

Monsheel S. K. Sodhi, David C. Airey, Warren Lambert, Philip W. J. Burnet, Paul J. Harrison and Elaine Sanders-Bush
Molecular Pharmacology September 1, 2005, 68 (3) 711-719; DOI: https://doi.org/10.1124/mol.105.014134
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