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Probenecid Reduces Alcohol Drinking in Rodents. Is Pannexin1 a Novel Therapeutic Target for Alcohol Use Disorder?
- Source :
-
Alcohol and alcoholism (Oxford, Oxfordshire) [Alcohol Alcohol] 2019 Jan 09; Vol. 54 (5), pp. 497-502. - Publication Year :
- 2019
-
Abstract
- Aims: The development of novel and more effective medications for alcohol use disorder (AUD) is an important unmet medical need. Drug repositioning or repurposing is an appealing strategy to bring new therapies to the clinic because it greatly reduces the overall costs of drug development and expedites the availability of treatments to those who need them. Probenecid, p-(di-n-propylsulfamyl)-benzoic acid, is a drug used clinically to treat hyperuricemia and gout due to its activity as an inhibitor of the kidneys' organic anion transporter that reclaims uric acid from urine. Probenecid also inhibits pannexin1 channels that are involved in purinergic neurotransmission and inflammation, which have been implicated in alcohol's effects and motivation for alcohol. Therefore, we tested the effects of probenecid on alcohol intake in rodents.<br />Methods: We tested the effects of probenecid on operant oral alcohol self-administration in alcohol-dependent rats during acute withdrawal as well as in nondependent rats and in the drinking-in-the-dark (DID) paradigm of binge-like drinking in mice.<br />Results: Probenecid reduced alcohol intake in both dependent and nondependent rats and in the DID paradigm in mice without affecting water or saccharin intake, indicating that probenecid's effect was selective for alcohol and not the result of a general reduction in reward.<br />Conclusions: These results raise the possibility that pannexin1 is a novel therapeutic target for the treatment of AUD. The clinical use of probenecid has been found to be generally safe, suggesting that it can be a candidate for drug repositioning for the treatment of AUD.<br /> (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)
- Subjects :
- Adjuvants, Pharmaceutic pharmacology
Adjuvants, Pharmaceutic therapeutic use
Alcohol Drinking metabolism
Alcohol Drinking psychology
Alcoholism metabolism
Alcoholism psychology
Animals
Connexins metabolism
Dose-Response Relationship, Drug
Male
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins metabolism
Probenecid pharmacology
Rats
Rats, Wistar
Self Administration
Alcohol Drinking drug therapy
Alcoholism drug therapy
Connexins antagonists & inhibitors
Drug Delivery Systems methods
Ethanol administration & dosage
Nerve Tissue Proteins antagonists & inhibitors
Probenecid therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3502
- Volume :
- 54
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Alcohol and alcoholism (Oxford, Oxfordshire)
- Publication Type :
- Academic Journal
- Accession number :
- 31535696
- Full Text :
- https://doi.org/10.1093/alcalc/agz054