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Neuromolecular and behavioral effects of ethanol deprivation in Drosophila

View ORCID ProfileNatalie M. D’Silva, Katie S. McCullar, Ashley Conard, Tyler Blackwater, Reza Azanchi, Ulrike Heberlein, Erica Larschan, Karla R. Kaun
doi: https://doi.org/10.1101/2021.01.02.425101
Natalie M. D’Silva
aDepartment of Neuroscience, Brown University, Providence, RI 02912
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Katie S. McCullar
aDepartment of Neuroscience, Brown University, Providence, RI 02912
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Ashley Conard
bComputer Science, Brown University, Providence, RI, 02906
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Tyler Blackwater
aDepartment of Neuroscience, Brown University, Providence, RI 02912
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Reza Azanchi
aDepartment of Neuroscience, Brown University, Providence, RI 02912
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Ulrike Heberlein
cJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147
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Erica Larschan
bComputer Science, Brown University, Providence, RI, 02906
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Karla R. Kaun
aDepartment of Neuroscience, Brown University, Providence, RI 02912
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  • For correspondence: karla_kaun@brown.edu
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Abstract

Alcohol use disorder (AUD) is characterized by loss of control in limiting alcohol intake. This may involve intermittent periods of abstinence followed by alcohol seeking and, consequently, relapse. However, little is understood of the molecular mechanisms underlying the impact of alcohol deprivation on behavior. Using a new Drosophila melanogaster repeated intermittent alcohol exposure model, we sought to identify how ethanol deprivation alters spontaneous behavior, determine the associated neural structures, and reveal correlated changes in brain gene expression. We found that repeated intermittent ethanol exposures followed by ethanol-deprivation dynamically induces behaviors associated with a negative affect state. Although behavioral states broadly mapped to many brain regions, persistent changes in social behaviors mapped to the mushroom body and surrounding neuropil. This occurred concurrently with changes in expression of genes associated with sensory responses, neural plasticity, and immunity. Like social behaviors, immune response genes were upregulated following three-day repeated intermittent ethanol-exposures and persisted with one or two days of ethanol-deprivation, suggesting an enduring change in molecular function. Our study provides a framework for identifying how ethanol deprivation alters behavior with correlated underlying circuit and molecular changes.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 04, 2021.
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Neuromolecular and behavioral effects of ethanol deprivation in Drosophila
Natalie M. D’Silva, Katie S. McCullar, Ashley Conard, Tyler Blackwater, Reza Azanchi, Ulrike Heberlein, Erica Larschan, Karla R. Kaun
bioRxiv 2021.01.02.425101; doi: https://doi.org/10.1101/2021.01.02.425101
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Neuromolecular and behavioral effects of ethanol deprivation in Drosophila
Natalie M. D’Silva, Katie S. McCullar, Ashley Conard, Tyler Blackwater, Reza Azanchi, Ulrike Heberlein, Erica Larschan, Karla R. Kaun
bioRxiv 2021.01.02.425101; doi: https://doi.org/10.1101/2021.01.02.425101

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