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The Journal of Neuroscience, November 1, 2002, 22(21):9490-9501

Functional Dissection of Neuroanatomical Loci Regulating Ethanol Sensitivity in Drosophila

Aylin R. Rodan1, 3, John A. Kiger Jr4, and Ulrike Heberlein1, 2, 3

1 Department of Anatomy and Programs in 2 Neuroscience and 3 Biological Sciences, University of California, San Francisco, California 94143-0452, and 4 Department of Molecular and Cellular Biology, University of California, Davis, California 95616

Ethanol has complex but similar effects on behavior in mammals and the fruit fly Drosophila melanogaster. In addition, genetic and pharmacological approaches have implicated the cAMP pathway in the regulation of ethanol-induced behaviors in both flies and rodents. Here we examine the neuroanatomical loci that modulate ethanol sensitivity in Drosophila by targeting the expression of an inhibitor of cAMP-dependent protein kinase (PKA) to specific regions in the fly's brain. Expression of the inhibitor in most brain regions or in muscle has no effect on behavior. In contrast, inhibition of PKA in a relatively small number of cells, possibly neurosecretory cells, in the fly's brain is sufficient to decrease sensitivity to the incoordinating effects of ethanol. Additional brain areas are, however, also involved. The mushroom bodies, brain structures where cAMP signaling is required for olfactory classical conditioning, are dispensable for the regulation of ethanol sensitivity. Finally, different behavioral effects of ethanol, motor incoordination and sedation, appear to be regulated by PKA function in distinct brain regions. We conclude that the regulation of ethanol-induced behaviors by PKA involves complex interactions among groups of cells that mediate either increased or reduced sensitivity to the acute intoxicating effects of ethanol.

Key words: Drosophila; ethanol; PKA; neuroanatomy; mushroom bodies; postural control; locomotion


Copyright © 2002 Society for Neuroscience  0270-6474/02/22219490-12$05.00/0


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