The potency of volatile anesthetics and n-alkanes as agents of general anesthesia has been determined in Drosophila melanogaster. The correlation of potency with hydrophobicity and the absolute concentration required to achieve anesthetic effects are similar to those reported in higher organisms. Thus, Drosophila has been confirmed as a suitable model system for study of the mechanism of general anesthesia. Several mutants of the fruit fly that are altered in their response to halothane have been studied further. One mutant loses its anesthetic resistance upon decapitation while three other mutants retain resistance. This analysis highlights the anatomic complexity of the anesthetic response. In another study, wild-type and mutant intact flies have been assessed in a time-independent assay of the escape from a noxious stimulus. This tail-flick assay for fruit flies shows that each mutant locus differentially affects the response to different anesthetics. The result argues against the hypothesis that all anesthetics interact in identical manner with the anesthetic target.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002228-07
Application #
3845220
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Burg, E D; Langan, S T; Nash, H A (2013) Drosophila social clustering is disrupted by anesthetics and in narrow abdomen ion channel mutants. Genes Brain Behav 12:338-47
Peabody, Nathan C; Pohl, Jascha B; Diao, Fengqiu et al. (2009) Characterization of the decision network for wing expansion in Drosophila using targeted expression of the TRPM8 channel. J Neurosci 29:3343-53
Sandstrom, David J (2008) Isoflurane reduces excitability of Drosophila larval motoneurons by activating a hyperpolarizing leak conductance. Anesthesiology 108:434-46
Cheng, Yuzhong; Nash, Howard A (2008) Visual mutations reveal opposing effects of illumination on arousal in Drosophila. Genetics 178:2413-6
Cheng, Yuzhong; Nash, Howard A (2007) Drosophila TRP channels require a protein with a distinctive motif encoded by the inaF locus. Proc Natl Acad Sci U S A 104:17730-4
Humphrey, John A; Hamming, Kevin S; Thacker, Colin M et al. (2007) A putative cation channel and its novel regulator: cross-species conservation of effects on general anesthesia. Curr Biol 17:624-9
Yu, James X; Guan, Zhonghui; Nash, Howard A (2006) The mushroom body defect gene product is an essential component of the meiosis II spindle apparatus in Drosophila oocytes. Genetics 173:243-53
Rajaram, Shantadurga; Scott, Robert L; Nash, Howard A (2005) Retrograde signaling from the brain to the retina modulates the termination of the light response in Drosophila. Proc Natl Acad Sci U S A 102:17840-5
Sandstrom, David J; Nash, Howard (2004) Drug targets: turning the channel (on) for sedation. Curr Biol 14:R185-6
Sandstrom, David J (2004) Isoflurane depresses glutamate release by reducing neuronal excitability at the Drosophila neuromuscular junction. J Physiol 558:489-502

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