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A DNA element regulates drug tolerance and withdrawal in Drosophila.

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 (?6b), 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.

SUBMITTER: Li X

PROVIDER: S-EPMC3781064 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A DNA element regulates drug tolerance and withdrawal in Drosophila.

Li Xiaolei X Ghezzi Alfredo A Pohl Jascha B JB Bohm Arun Y AY Atkinson Nigel S NS

PloS one 20130923 9

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 responsi ...[more]

PMID: 24086565

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