Affiliation: California State University, Northridge, Los Angeles, CA
Keywords: t. other (ethanol sensitivity/resistance); t. other (transmission of drug tolerance)
Characterization of the mode of transmission of ethanol resistance to progeny of repeatedly intoxicated parental fliesThere has been a renewed interest in the transmission of acquired traits, particularly those related to tolerance to drugs and environmental toxins. Since tolerance is an accepted pre-requisite and strong predictor of addiction, a firmer understanding of the mechanisms underlying the transmission of tolerance could facilitate novel research avenues of importance in public health. Despite the significant advances made in characterizing the epigenetic and molecular mechanisms that underlie the transmission of acquired traits across diverse species, it is still unclear what genetic pathways may connect acquired traits that operate primarily in metabolic, physiologic or nervous system levels with the necessary epigenetic modifications in the germline for transmission to take place. While classic model organisms, such D. melanogaster and C. elegans are prime candidates to dissect conserved aspects of the genetic and epigenetic underpinnings of acquired trait inheritance, little is known about their capacity to transmit acquired drug tolerance to their progeny.
Numerous previous studies over the last 20 years have demonstrated that fruit flies can develop tolerance to ethanol when repeatedly exposed to the drug. We have recently reported that parental flies that are intoxicated multiple times (once a day, for 10 minutes, over a 2 weeks period) give rise to progeny that is significantly more resistant to the sedative effects of ethanol. We observed that parental flies need to be exposed multiple times before transmission of resistance to progeny can be observed, that there is residual transmission of tolerance to the F2 and that the ability of females to transmit tolerance to their F1 progeny lasts several days after their last intoxicating exposure to ethanol. We have since more carefully explored whether the transmission of resistance to progeny of repeatedly intoxicated flies is matrilineal, patrilineal or both, which will delineate future research efforts aimed at elucidating the genetic and molecular bases of the transmission. Overall, our findings present D. melanogaster as a suitable experimental model for forward and reverse genetics approaches to investigate the pathways connecting repeated exposures of an adult animal to ethanol and the necessary germline modifications that underlie the transmission of increased resistance in their progeny to the drug.