Inhibition of Glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats.
Pharmacology Biochemistry and Behavior. 2018-04-01; 167: 36-41
DOI: 10.1016/j.pbb.2018.03.001
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de Guglielmo G(1), Conlisk DE(2), Barkley-Levenson AM(3), Palmer AA(4), George O(5).
Author information:
(1)Department of Neuroscience, The Scripps Research Institute, La Jolla, CA
92037, USA. Electronic address: .
(2)Department of Neuroscience, The Scripps Research Institute, La Jolla, CA
92037, USA.
(3)Department of Psychiatry, University of California San Diego, La Jolla, CA
92037, USA.
(4)Department of Psychiatry, University of California San Diego, La Jolla, CA
92037, USA; Institute for Genomic Medicine, University of California San Diego,
La Jolla, CA 92037, USA.
(5)Department of Neuroscience, The Scripps Research Institute, La Jolla, CA
92037, USA. Electronic address: .
Previous studies showed that the glyoxalase 1 (Glo1) gene modulates anxiety-like
behavior, seizure susceptibility, depression-like behavior, and alcohol drinking
in the drinking-in-the-dark paradigm in nondependent mice. Administration of the
small-molecule GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG)
decreased alcohol drinking in nondependent mice, suggesting a possible
therapeutic strategy. However, the preclinical therapeutic efficacy of pBBG in
animal models of alcohol dependence remains to be demonstrated. We tested the
effect of pBBG (7.5 and 25 mg/kg) on operant alcohol self-administration in
alcohol-dependent and nondependent rats. Wistar rats were trained to
self-administer 10% alcohol (v/v) and made dependent by chronic intermittent
passive exposure to alcohol vapor for 5 weeks. Pretreatment with pBBG
dose-dependently reduced alcohol self-administration in both nondependent and
dependent animals, without affecting water self-administration. pBBG treatment
was more effective in dependent rats than in nondependent rats. These data extend
previous findings that implicated Glo1 in alcohol drinking in nondependent mice
by showing even more profound effects in alcohol-dependent rats. These results
suggest that the pharmacological inhibition of GLO1 is a relevant therapeutic
target for the treatment of alcohol use disorders.
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