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Title:
γ-Aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: Adult RNA interference and pharmacological evidence
Authors:
Dzitoyeva, Svetlana; Dimitrijevic, Nikola; Manev, Hari
Affiliation:
AA(Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, IL 60612), AB(Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, IL 60612), AC(Department of Psychiatry, Psychiatric Institute, University of Illinois, Chicago, IL 60612)
Publication:
Proceedings of the National Academy of Sciences of the United States of America, Volume 100, Issue 9, 2003, pp.5485-5490
Publication Date:
04/2003
Category:
Neuroscience
Origin:
PNAS
DOI:
10.1073/pnas.0830111100
Bibliographic Code:
2003PNAS..100.5485D

Abstract

In addition to their physiological function, metabotropic receptors for neurotransmitter γ-aminobutyric acid (GABA), the GABAB receptors, may play a role in the behavioral actions of addictive compounds. Recently, GABAB receptors were cloned in fruit flies (Drosophila melanogaster), indicating that the advantages of this experimental model could be applied to GABAB receptor research. RNA interference (RNAi) is an endogenous process triggered by double-stranded RNA and is being used as a tool for functional gene silencing and functional genomics. Here we show how cell-nonautonomous RNAi can be induced in adult fruit flies to silence a subtype of GABAB receptors, GABABR1, and how RNAi combined with pharmacobehavioral techniques (including intraabdominal injections of active compounds and a computer-assisted quantification of behavior) can be used to functionally characterize these receptors. We observed that injection of double-stranded RNA complementary to GABABR1 into adult Drosophila selectively destroys GABABR1 mRNA and attenuates the behavioral actions of the GABAB agonist, 3-aminopropyl-(methyl)phosphinic acid. Moreover, both GABABR1 RNAi and the GABAB antagonist CGP 54626 reduced the behavior-impairing effects of ethanol, suggesting a putative role for the Drosophila GABAB receptors in alcohol's mechanism of action. The Drosophila model we have developed can be used for further in vivo functional characterization of GABAB receptor subunits and their involvement in the molecular and systemic actions of addictive substances.
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