Journal
JOURNAL OF NEUROSCIENCE
Volume 39, Issue 45, Pages 8877-8884Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0973-19.2019
Keywords
addiction; alcohol; Drosophila; genetics
Categories
Funding
- Universityof Utah Neuroscience Initiative
- [NIHT32DA007290]
- [F31AA021340]
- [AHA16CSA28530002]
- [NIHR01DK110358]
- [NIH R01AA019526]
- [U2M2]
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Alcohol use is highly prevalent in the United States and across the world, and every year millions of people suffer from alcohol use disorders (AUDs). Although the genetic contribution to developing AUDs is estimated to be 50-60%, many of the underlying molecular mechanisms remain unclear. Previous studies from our laboratory revealed that Drosophila melanogaster lacking RhoGAP18B and Ras Suppressor 1 (Rsu1) display reduced sensitivity to ethanol-induced sedation. Both Rsu1 and RhoGAP18B are negative regulators of the small Rho-family GTPase, Rac1, a modulator of actin dynamics. Here we investigate the role of Rac1 and its downstream target, the actin-severing protein cofilin, in alcohol consumption preference. We show that these two regulators of actin dynamics can alter male experience-dependent alcohol preference in a bidirectional manner: expressing either activated Rac1 or dominant-negative cofilin in the mushroom bodies (MBs) abolishes experience-dependent alcohol preference. Conversely, dominant-negative Rac1 or activated cofilin MB expression lead to faster acquisition of alcohol preference. Our data show that Rac1 and cofilin activity are key to determining the rate of acquisition of alcohol preference, revealing a critical role of actin dynamics regulation in the development of voluntary self-administration in Drosophila.
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