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Circadian Genes Differentially Affect Tolerance to Ethanol in D rosophila
Author(s) -
Pohl Jascha B.,
Ghezzi Alfredo,
Lew Linda K.,
Robles Roseanna B.,
Cormack Lawrence,
Atkinson Nigel S.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12173
Subject(s) - circadian rhythm , circadian clock , biology , alcohol tolerance , drosophila melanogaster , bacterial circadian rhythms , mutant , genetics , period (music) , drug tolerance , microbiology and biotechnology , gene , ethanol , endocrinology , biochemistry , pharmacology , physics , acoustics
Background There is a strong relationship between circadian rhythms and ethanol ( E t OH ) responses. EtOH consumption has been shown to disrupt physiological and behavioral circadian rhythms in mammals ( A lcohol C lin E xp R es 2005b, 29, 1550). The D rosophila central circadian pacemaker is composed of proteins encoded by the per , tim , cyc , and C lk genes. Using D rosophila mutant analysis, we asked whether these central components of the circadian clock make the equivalent contribution toward E t OH tolerance and whether rhythmicity itself is necessary for tolerance. Methods We tested flies carrying mutations in core clock genes for the capacity to acquire E t OH tolerance. Tolerance was assayed by comparing the sedation curves of populations during their first and second sedation. Animals that had acquired tolerance sedated more slowly. Movement was also monitored as the flies breathe the E t OH vapor to determine if other facets of the E t OH response were affected by the mutations. Gas chromatography was used to measure internal E t OH concentration. Constant light was used to nongenetically destabilize the PER and TIM proteins. Results A group of circadian mutations, all of which eliminate circadian rhythms, do not disrupt tolerance identically. Mutations in per , tim , and cyc completely block tolerance. However, a mutation in C lk does not interfere with tolerance. Constant light also disrupts the capacity to acquire tolerance. These lines did not differ in E t OH absorption. Conclusions Mutations affecting different parts of the intracellular circadian clock can block the capacity to acquire rapid E t OH tolerance. However, the role of circadian genes in E t OH tolerance is independent of their role in producing circadian rhythmicity. The interference in the capacity to acquire E t OH tolerance by some circadian mutations is not merely a downstream effect of a nonfunctional circadian clock; instead, these circadian genes play an independent role in E t OH tolerance.