Abstract
In humans, there is a strong correlation between sensitivity to substances of abuse and addiction risk. This differential tolerance to drugs has a strong genetic component. The identification of human genetic factors that alter drug tolerance has been a difficult task. For this reason and taking advantage of the fact that Drosophila responds similarly to humans to many drugs, and that genetically it has a high degree of homology (sharing at least 70% of genes known to be involved in human genetic diseases), we looked for genes in Drosophila that altered their nicotine sensitivity. We developed an instantaneous nicotine vaporization technique that exposed flies in a reproducible way. The amount of nicotine sufficient to “knock out” half of control flies for 30 minutes was determined and this parameter was defined as Half Recovery Time (HRT). Two fly lines, L4 and L70, whose HRT was significantly longer than control´s were identified. The L4 insertion is a loss of function allele of the transcriptional factor escargot (esg), whereas L70 insertion causes miss-expression of the microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate that esg loss of function induces nicotine sensitivity possibly by altering development of sensory organs and neurons in the medial section of the thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and possibly to the modulation of other miR-310c targets.
Highlights
Nicotine addiction is a serious public health problem
In order to determine the standard amount of nicotine to be used, we treated w1118 flies with different quantities of nicotine diluted in water to identify the sufficient amount of volatilized nicotine that allows half of the exposed flies to recover in 30 min
Line w1118 was used as control and reference line, because it is the genetic background of the P{GawB} insertion collection and of all the other lines used in this work, Oregon-R was used as an independent wt line and behaved identically to w1118 strongly suggesting that this is the wt sensitivity to nicotine (Fig 1A)
Summary
Nicotine addiction is a serious public health problem. Several studies in humans have provided evidence that there is a strong genetic component underlying nicotine and other substances addiction.Assessing the genetic contribution to addiction in humans is, to say the least, complicated. Nicotine addiction is a serious public health problem. Several studies in humans have provided evidence that there is a strong genetic component underlying nicotine and other substances addiction. Assessing the genetic contribution to addiction in humans is, to say the least, complicated. It is very difficult to separate the environmental contribution from the genetic effects; PLOS ONE | DOI:10.1371/journal.pone.0133956. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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