Antagonism of Sigma‐1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice

Autor: Pietro Cottone, Sean M Tanino, Yasmine N Sami, Malliga R. Iyer, Valentina Sabino, Sema G. Quadir, Kenner C. Rice, Margaret A. Minnig
Rok vydání: 2021
Předmět:
Zdroj: Alcohol Clin Exp Res
ISSN: 1530-0277
0145-6008
DOI: 10.1111/acer.14635
Popis: BACKGROUND Alcohol use disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma-1 receptors (Sig-1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig-1R hyperactivity may result in excessive alcohol drinking. Sig-1R studies in mice are very scarce, and its potential role in alcohol-induced hyperalgesia is also unknown. METHODS In this study, we investigated the role of Sig-1R in alcohol drinking and associated hyperalgesia in male mice, using an intermittent access 2-bottle choice model of heavy drinking. RESULTS The Sig-1R antagonist BD-1063 was found dose dependently to reduce both alcohol intake and preference, without affecting either water or sucrose intake, suggesting that the effects are specific for alcohol. Notably, the ability of BD-1063 to suppress ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking animals. In addition, BD-1063 reversed alcohol-induced hyperalgesia during withdrawal, assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol-naive animals or locomotor activity in either group. CONCLUSIONS These data show that Sig-1R antagonism dose-dependently reduced ethanol consumption in heavy drinking mice as well as its efficacy in reducing alcohol-induced hyperalgesia. These findings provide a foundation for the development of novel treatments for AUD and associated pain states.
Databáze: OpenAIRE
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