Referenced in: none

Automatically associated channels: Slo1

Title: A DNA element regulates drug tolerance and withdrawal in Drosophila.

Authors: Xiaolei Li, Alfredo Ghezzi, Jascha B Pohl, Arun Y Bohm, Nigel S Atkinson

Journal, date & volume: PLoS ONE, 2013 , 8, e75549

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24086565

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.