A DNA element regulates drug tolerance and withdrawal in Drosophila.
PLoS One
; 8(9): e75549, 2013.
Article
em En
| MEDLINE
| ID: mdl-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.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
/
Drosophila
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article