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
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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