Li, X., Ghezzi, A., Pohl, J.B., Bohm, A.Y., Atkinson, N.S. (2013). A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila. PLoS ONE 8(9): e75549.
FlyBase ID
FBrf0222906
Publication Type
Research paper
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.
