Normal Ethanol Sensitivity and Rapid Tolerance Require the G Protein Receptor Kinase 2 in Ellipsoid Body Neurons in Drosophila

Authors

Yuan Yuan Kang, University of Houston-Downtown
Yusuke Wachi, University of Mississippi
Elizabeth Engdorf, University of Houston-Downtown
Emiliano Fumagalli, University of Houston
Youyou Wang, University of Houston
Jennifer Myers, University of Houston
Shebna Massey, University of Houston-Downtown
Antony Greiss, University of Houston-Downtown
Shiyu Xu, University of Houston
Gregg Roman, University of Mississippi

Document Type

Article

Publication Date

8-1-2020

Abstract

© 2020 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism Background: G protein signaling pathways are key neuromodulatory mechanisms for behaviors and neurological functions that affect the impact of ethanol (EtOH) on locomotion, arousal, and synaptic plasticity. Here, we report a novel role for the Drosophila G protein–coupled receptor kinase 2 (GPRK2) as a member of the GRK4/5/6 subfamily in modulating EtOH-induced behaviors. Methods: We studied the requirement of Drosophila Gprk2 for naïve sensitivity to EtOH sedation and ability of the fly to develop rapid tolerance after a single exposure to EtOH, using the loss of righting reflex (LORR) and fly group activity monitor (FlyGrAM) assays. Results: Loss-of-function Gprk2 mutants demonstrate an increase in alcohol-induced hyperactivity, reduced sensitivity to the sedative effects of EtOH, and diminished rapid tolerance after a single intoxicating exposure. The requirement for Gprk2 in EtOH sedation and rapid tolerance maps to ellipsoid body neurons within the Drosophila brain, suggesting that wild-type Gprk2 is required for modulation of locomotion and alertness. However, even though Gprk2 loss of function leads to decreased and fragmented sleep, this change in the sleep state does not depend on Gprk2 expression in the ellipsoid body. Conclusion: Our work on GPRK2 has established a role for this GRK4/5/6 subfamily member in EtOH sensitivity and rapid tolerance.

Relational Format

journal article

Recommended Citation

Kang, Y.Y., Wachi, Y., Engdorf, E., Fumagalli, E., Wang, Y., Myers, J., Massey, S., Greiss, A., Xu, S. and Roman, G. (2020), Normal Ethanol Sensitivity and Rapid Tolerance Require the G Protein Receptor Kinase 2 in Ellipsoid Body Neurons in Drosophila. Alcohol Clin Exp Res, 44: 1686-1699. https://doi.org/10.1111/acer.14396

DOI

10.1111/acer.14396

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