Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for regulation by the cAMP signaling pathway.
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.
Moore
M S
MS
Gallo Center and Department of Neurology, University of California, San Francisco, 94110, USA. sieh@itsa.ucsf.edu
DeZazzo
J
J
Luk
A Y
AY
Tully
T
T
Singh
C M
CM
Heberlein
U
U
D000262:Adenylyl Cyclases / Q000378:metabolism; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001522:Behavior, Animal; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D017344:Genes, Insect / Q000235:genetics; D005816:Genetic Complementation Test; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D012333:RNA, Messenger; C093565:amn protein, Drosophila; C112891:cheapdate protein, Drosophila; D005576:Colforsin; D000431:Ethanol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases