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

BACKGROUND Alcohol Use Disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as by 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 to dose-dependently 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 in suppressing ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking subjects. In addition, BD-1063 was able to reverse alcohol-induced hyperalgesia during withdrawal, as assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol-naïve animals or locomotor activity in either group. CONCLUSIONS These data show anti-alcohol effects of Sig-1R antagonism in heavy drinking mice as well as its efficacy in reducing alcohol-induced hyperalgesia, thereby laying the foundation for the development of novel treatments for AUD and associated pain states.

• Publication year

  2021

• Venue

  Alcoholism: Clinical and Experimental Research

• Publication date

  2021-05-31

• Fields of study

  Medicine

• Identifiers
  DOI 10.1111/acer.14635PMID 34060104PMCID PMC8295198
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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