BioProject

The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. More...

The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Whereas environmental factors, such as stress and social experience, contribute to individual variation in sensitivity to chronic alcohol consumption, genetic factors have also been implicated. However, genetic polymorphisms that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of olfactory sensitivity and, concomitant with development of tolerance, altered transcription of enzymes associated with fatty acid biosynthesis. Our results identify key enzymes in conserved metabolic pathways that may contribute to human alcohol sensitivity. Keywords: Drosophila, model system, alcohol sensitivity, tolerance Overall design: Alcohol sensitivity in Drosophila melanogaster can be quantified in an inebriometer. The elution time from the column is used as a measure of sensitivity to alcohol intoxication. Overall design: We collected 3-5 day old Canton S flies either without exposure to ethanol (control group), immediately after passage through the inebriometer, or from a population that had developed tolerance 2h after the initial ethanol exposure. Less...