UCSF

Ethanol is one of the most widely used and abused drugs in the world. Ethanol consumption produces short-term changes in behavior as well as long-term adaptations that can lead to addiction. The mechanisms underlying both acute and chronic responses to ethanol are still not fully understood. Human and rodent studies have suggested that acute ethanol sensitivity may be related to risk of alcohol abuse, and that the same genes often regulate both types of behavior. In this thesis I have used the fruit fly Drosophila melanogaster as a model to study the genetic and neural mechanisms underlying ethanol-induced behavior.

In Chapter 2, I show that flies prefer to consume food containing ethanol and that this ethanol preference may represent a new model for studying addiction-related behavior. In Chapter 3, I examine the relationships between acute ethanol sensitivity, ethanol tolerance, and ethanol consumption preference by measuring these behaviors in a set of Drosophila mutants. I found that ethanol tolerance and preference were positively correlated, suggesting that the development of tolerance might be one factor contributing to the increase in ethanol consumption that we observe over time. Finally, in Chapter 4 I characterize sex differences in acute ethanol responses in Drosophila, which also occur in humans. I identify two genes, fruitless and tank, that regulate ethanol responses in a sexually dimorphic manner, and I show that these genes define distinct sets of neurons that interact to regulate ethanol sensitivity. Overall, this work has helped to expand the repertoire of behavioral assays available to study ethanol-related behavior in flies, shed light on the relationships between different ethanol-induced behaviors, and identified two new genes and corresponding sets of neurons that regulate acute ethanol responses.