A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.

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Sodhi MS, Airey DC, Lambert W, Burnet PW, Harrison PJ, Sanders-Bush E

A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.

Mol Pharmacol. 2005 Sep;68(3):711-9. Epub 2005 May 25.

PubMed ID

15917433 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clozapine	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Antagonist	Details