1. Ethanol Intoxication in Drosophila: Genetic and Pharmacological Evidence for Regulation by the cAMP Signaling Pathway
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Tim Tully, Alvin Y. Luk, Ulrike Heberlein, Jim DeZazzo, Carol M. Singh, and Monica S. Moore
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Male ,medicine.medical_specialty ,Mutant ,Molecular Sequence Data ,Neuropeptide ,Genes, Insect ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Animals, Genetically Modified ,03 medical and health sciences ,Enzyme activator ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Cyclic AMP ,Animals ,Drosophila Proteins ,Amino Acid Sequence ,RNA, Messenger ,Ethanol metabolism ,Cloning, Molecular ,Enzyme Inhibitors ,Alleles ,030304 developmental biology ,0303 health sciences ,Ethanol ,Base Sequence ,Behavior, Animal ,Biochemistry, Genetics and Molecular Biology(all) ,Colforsin ,Genetic Complementation Test ,Neuropeptides ,Cyclic AMP-Dependent Protein Kinases ,Cell biology ,Enzyme Activation ,Endocrinology ,Drosophila melanogaster ,chemistry ,Mutation ,cAMP-dependent pathway ,Signal transduction ,030217 neurology & neurosurgery ,Drosophila Protein ,Adenylyl Cyclases ,Signal Transduction - Abstract
Upon exposure to ethanol, Drosophila display behaviors that are similar to ethanol intoxication in rodents and humans. Using an inebriometer to measure ethanol-induced loss of postural control, we identified cheapdate, a mutant with enhanced sensitivity to ethanol. Genetic and molecular analyses revealed that cheapdate is an allele of the memory mutant amnesiac. amnesiac has been postulated to encode a neuropeptide that activates the cAMP pathway. Consistent with this, we find that enhanced ethanol sensitivity of cheapdate can be reversed by treatment with agents that increase cAMP levels or PKA activity. Conversely, genetic or pharmacological reduction in PKA activity results in increased sensitivity to ethanol. Taken together, our results provide functional evidence for the involvement of the cAMP signal transduction pathway in the behavioral response to intoxicating levels of ethanol.
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