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Article

Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice

1
Department of Psychiatry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
2
Institute for Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Claudio D’Addario
Brain Sci. 2021, 11(1), 127; https://doi.org/10.3390/brainsci11010127
Received: 20 November 2020 / Revised: 13 January 2021 / Accepted: 15 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue The Genetics of Alcohol Use Disorder)
Central nervous system (CNS) hyperexcitability is a clinically significant feature of acute ethanol withdrawal. There is evidence for a genetic contribution to withdrawal severity, but specific genetic risk factors have not been identified. The gene glyoxalase 1 (Glo1) has been previously implicated in ethanol consumption in mice, and GLO1 inhibition can attenuate drinking in mice and rats. Here, we investigated whether genetic and pharmacological manipulations of GLO1 activity can also mediate ethanol withdrawal seizure severity in mice. Mice from two transgenic lines overexpressing Glo1 on different genetic backgrounds (C57BL/6J (B6) and FVB/NJ (FVB)) were tested for handling-induced convulsions (HICs) as a measure of acute ethanol withdrawal. Following an injection of 4 g/kg alcohol, both B6 and FVB mice overexpressing Glo1 showed increases in HICs compared to wild-type littermates, though only the FVB line showed a statistically significant difference. We also administered daily ethanol injections (2 g/kg + 9 mg/kg 4-methylpyrazole) to wild-type B6 mice for 10 days and tested them for HICs on the 10th day following treatment with either a vehicle or a GLO1 inhibitor (S-bromobenzylglutathione cyclopentyl diester (pBBG)). Treatment with pBBG reduced HICs, although this effect was only statistically significant following two 10-day cycles of ethanol exposure and withdrawal. These results provide converging genetic and pharmacological evidence that GLO1 can mediate ethanol withdrawal seizure susceptibility. View Full-Text
Keywords: ethanol; withdrawal; genetics; handling induced convulsions; glyoxalase 1 ethanol; withdrawal; genetics; handling induced convulsions; glyoxalase 1
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MDPI and ACS Style

Barkley-Levenson, A.M.; Lee, A.; Palmer, A.A. Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice. Brain Sci. 2021, 11, 127. https://doi.org/10.3390/brainsci11010127

AMA Style

Barkley-Levenson AM, Lee A, Palmer AA. Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice. Brain Sciences. 2021; 11(1):127. https://doi.org/10.3390/brainsci11010127

Chicago/Turabian Style

Barkley-Levenson, Amanda M., Amy Lee, and Abraham A. Palmer 2021. "Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice" Brain Sciences 11, no. 1: 127. https://doi.org/10.3390/brainsci11010127

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