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PLoS One. 2013 Sep 23;8(9):e75549. doi: 10.1371/journal.pone.0075549. eCollection 2013.

A DNA element regulates drug tolerance and withdrawal in Drosophila.

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  • 1The Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology, the University of Texas at Austin, Austin, Texas, United States of America.

Abstract

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 Ca(2+) 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, slo (Δ6b), 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.

PMID:
24086565
PMCID:
PMC3781064
DOI:
10.1371/journal.pone.0075549
[PubMed - indexed for MEDLINE]
Free PMC Article
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