The foraging gene affects alcohol sensitivity, metabolism and memory in Drosophila

Abstract

The genetic basis of alcohol use disorder (AUD) is complex. Understanding how natural genetic variation contributes to alcohol phenotypes can help us identify and understand the genetic basis of AUD. Recently, a single nucleotide polymorphism in the human foraging (for) gene ortholog, Protein Kinase cGMP-Dependent 1 (PRKG1), was found to be associated with stress-induced risk for alcohol abuse. However, the mechanistic role that PRKG1 plays in AUD is not well understood. We use natural variation in the Drosophila for gene to describe how variation of cGMP-dependent protein kinase (PKG) activity modifies ethanol-induced phenotypes. We found that variation in for affects ethanol-induced increases in locomotion and memory of the appetitive properties of ethanol intoxication. Further, these differences may stem from the ability to metabolize ethanol. Together, this data suggests that natural variation in PKG modulates cue reactivity for alcohol, and thus could influence alcohol cravings by differentially modulating metabolic and behavioral sensitivities to alcohol.

Keywords:

• Foraging
• PRKG1
• cGMP-dependent protein kinase
• alcohol
• memory
• metabolism
• locomotion
• AUD
• Drosophila

Acknowledgements

We would like to thank Dr. Ulrike Heberlein (Janelia Research Campus) for helpful early discussions about the alcohol-associated preference and metabolism data. Thanks to Dr. Kristin Branson (Janelia Research Campus), Dr. Alice Robie (Janelia Research Campus), Dr. Mayank Kabra (Janelia Research Campus) and members of the Ctrax and JAABA google groups for ongoing assistance with Ctrax and JAABA. Thanks to members of the Kaun Lab and Dr. Kristin Scaplen (Bryant University) for providing helpful feedback on data visualization, analysis, and writing. Thanks to Dr. Marla Sokolowski (University of Toronto) for providing the for strains.

With gratitude to Dr. Marla Sokolowski: Thanks especially to Dr. Marla Sokolowski, whose guidance was integral to the conceptualization of this work. It is the people that we work with, including incredible mentors like Marla, that help shape us as scientists. Marla has been a huge inspiration to me (Karla), and more broadly an entire generation of behavioral geneticists. Her contributions have made an important and indelible mark on the field. I’m extremely grateful to her for her rigorous scientific training and continued patience, encouragement and immense knowledge. Marla is a lifelong mentor, and I consider myself incredibly fortunate to have the opportunity to conduct a study related to her research in my own lab. I’m delighted this work will join several other similar and relevant papers highlighting the important contributions of Marla in this special edition of Journal of Neurogenetics. This work was completed with immense gratitude to Marla, for setting the stage and making it possible for generations of scientists to use foraging as an example of how natural genetic variation affects behavior. We all thank-you Marla, for being the amazing mentor and scientist that you are.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by the National Institutes of Health [R01AA024434 to K.R.K].