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dc.creatorLi, Xiaoleien
dc.creatorGhezzi, Alfredoen
dc.creatorPohl, Jascha B.en
dc.creatorBohm, Arun Y.en
dc.creatorAtkinson, Nigel S.en
dc.date.accessioned2014-12-15T17:09:37Zen
dc.date.available2014-12-15T17:09:37Zen
dc.date.issued2013-09-23en
dc.identifier.citationLi X, Ghezzi A, Pohl JB, Bohm AY, Atkinson NS (2013) A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila. PLoS ONE 8(9): e75549. doi:10.1371/journal.pone.0075549en
dc.identifier.urihttp://hdl.handle.net/2152/27780en
dc.descriptionen
dc.description.abstractDrug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca2+ activated K+ channel gene. After drug clearance this change produces a withdrawal phenotype—increased seizure susceptibility. The drug-induced histone modification profile identified the 6b element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the allele, sloΔ6b, that reacts more strongly to the drug with increased induction, a massive increase in the duration of tolerance, and an increase in the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b element is a homeostatic regulator of BK channel gene expression and is the first cis-acting DNA element shown to specifically affect the duration of a drug action.en
dc.description.sponsorshipThis work has been supported by National Institutes of Health (NIH) R01 AA018037 (subgroup: NIAAA, title: Epigenetic Modification as a Mechanism to Produce Functional Tolerance). URL: http://www.niaaa.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.language.isoEnglishen
dc.publisherPLOS Oneen
dc.rightsAdministrative deposit of works to UT Digital Repository: This works author(s) is or was a University faculty member, student or staff member; this article is already available through open access at http://www.plosone.org. The public license is specified as CC-BY: http://creativecommons.org/licenses/by/4.0/. The library makes the deposit as a matter of fair use (for scholarly, educational, and research purposes), and to preserve the work and further secure public access to the works of the University.en
dc.subjectalcoholsen
dc.subjectcalcium-activated potassium channelsen
dc.subjectepileptic seizuresen
dc.subjectmutationen
dc.subjectphenotypeen
dc.subjectpolymerase chain reactionen
dc.subjectsedativesen
dc.titleA DNA Element Regulates Drug Tolerance and Withdrawal in Drosophilaen
dc.typeArticleen
dc.description.departmentWaggoner Center for Alcohol and Addiction Researchen
dc.description.catalogingnoteEmail: NigelA@mail.utexas.eduen
dc.identifier.Filenamejournal.pone.0075549.pdfen
dc.identifier.doiDOI: 10.1371/journal.pone.0075549en


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