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Nonphosphorylatable Src Ser75 Mutation Increases Ethanol Preference and Consumption in Mice
1Department of Biochemistry, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi 409-3898, Japan.
Eneuro
|April 10, 2019
Summary
Src phosphorylation at Ser75 influences alcohol consumption. Nonphosphorylatable Src mutants increased ethanol preference, suggesting Src
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Src is a kinase highly expressed in CNS neurons, involved in development and brain functions, including alcohol consumption.
- Src knockout mice show developmental defects, limiting behavioral studies in adults.
- Src's unique domain phosphorylation at Ser75 by Cdk1/Cdk5 affects neuronal function.
Purpose of the Study:
- To investigate the role of Src phosphorylation at Ser75 in regulating voluntary ethanol consumption.
- To examine how nonphosphorylatable (Ser75Ala) and phosphomimetic (Ser75Asp) Src mutants affect ethanol intake and related behaviors.
Main Methods:
- Generation and analysis of mice harboring Ser75Ala or Ser75Asp Src mutants.
- Measurement of ethanol preference and consumption.
- Assessment of plasma ethanol concentrations and sedative effects.
- Analysis of Rho-associated kinase (ROCK) activity and Akt phosphorylation in the striatum.
Main Results:
- Mice with the Ser75Ala Src mutant showed significantly higher preference and consumption of ethanol solutions compared to wild-type mice.
- No differences in plasma ethanol levels or sedative sensitivity were observed between groups.
- The Ser75Ala mutant mice exhibited lower striatal ROCK activity and higher Akt Ser473 phosphorylation.
Conclusions:
- Src regulates voluntary ethanol drinking in a manner dependent on Ser75 phosphorylation.
- Specific phosphorylation of Src at Ser75 is critical for modulating alcohol consumption behaviors.
- Altered ROCK activity and Akt phosphorylation in the striatum may underlie the observed changes in ethanol intake.
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