Academic Journal

A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila

التفاصيل البيبلوغرافية
العنوان: A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila
المؤلفون: Li, Xiaolei, Ghezzi, Alfredo, Pohl, Jascha B., Bohm, Arun Y., Atkinson, Nigel S.
بيانات النشر: PLOS One
سنة النشر: 2013
المجموعة: The University of Texas at Austin: Texas ScholarWorks
مصطلحات موضوعية: alcohols, calcium-activated potassium channels, epileptic seizures, mutation, phenotype, polymerase chain reaction, sedatives
الوصف: Drug 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. ; This 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. ; Waggoner Center for Alcohol and Addiction Research ; Email: NigelA@mail.utexas.edu
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
Relation: Li 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.0075549; http://hdl.handle.net/2152/27780; journal.pone.0075549.pdf
DOI: 10.1371/journal.pone.0075549
الاتاحة: http://hdl.handle.net/2152/27780
https://doi.org/10.1371/journal.pone.0075549
Rights: Administrative 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.
رقم الانضمام: edsbas.147ED7E2
قاعدة البيانات: BASE
الوصف
DOI:10.1371/journal.pone.0075549