A DNA Element Regulates Drug Tolerance and Withdrawal in Drosophila




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

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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.


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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