11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse
Autor: | Amanda J. Roberts, Tomoya Kawamura, Pietro Paolo Sanna, Leandro F. Vendruscolo, Jihuan Chen, George F. Koob, Vez Repunte-Canonigo |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
endocrine system Alcohol Drinking Carbenoxolone Drinking Behavior Binge drinking Alcohol abuse Self Administration Alcohol Pharmacology Choice Behavior Binge Drinking Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine 11-beta-Hydroxysteroid Dehydrogenase Type 2 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Animals Rats Wistar Biological Psychiatry Ethanol Behavior Animal business.industry Central Nervous System Depressants medicine.disease Rats 3. Good health Mice Inbred C57BL Alcoholism Disease Models Animal Psychiatry and Mental health 030104 developmental biology chemistry Conditioning Operant Original Article Psychopharmacology Gastritis medicine.symptom business 030217 neurology & neurosurgery Glucocorticoid medicine.drug |
Zdroj: | Translational Psychiatry |
ISSN: | 2158-3188 |
Popis: | The identification of new and more effective treatments for alcohol abuse remains a priority. Alcohol intake activates glucocorticoids, which have a key role in alcohol's reinforcing properties. Glucocorticoid effects are modulated in part by the activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) acting as pre-receptors. Here, we tested the effects on alcohol intake of the 11β-HSD inhibitor carbenoxolone (CBX, 18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively used in the clinic for the treatment of gastritis and peptic ulcer and is active on both 11β-HSD1 and 11β-HSD2 isoforms. We observed that CBX reduces both baseline and excessive drinking in rats and mice. The CBX diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which we found to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors may be a promising new class of candidate alcohol abuse medications, and existing 11β-HSD inhibitor drugs may be potentially re-purposed for alcohol abuse treatment. |
Databáze: | OpenAIRE |
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