Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE

Sheena Potretzke, Yangmiao Zhang, Ju Li, Kristopher M. Fecteau, David Erikson, Marcel Hibert, Andrey E. Ryabinin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Targeting the oxytocin (OXT) peptide system has emerged as a promising new approach for the treatment of alcohol use disorder (AUD). However, further advancements in this development depend on properly modeling various complex social aspects of AUD and its treatment. Here we examined behavioral and molecular underpinnings of OXT receptor (OXTR) agonism in prairie voles, a rodent species with demonstrated translational validity for neurobiological mechanisms regulating social affiliations. To further improve translational validity of these studies, we examined effects of intranasal (IN) OXT administration in male and female prairie voles socially housed in the presence of untreated cagemates. IN OXT selectively inhibited alcohol drinking in male, but not female, animals. Further, we confirmed that exogenously administered OXT penetrates the prairie vole brain and showed that Receptor for Advanced Glycation End-products assists this penetration after IN, but not intraperitoneal (IP), OXT administration. Finally, we demonstrated that IP administration of LIT-001, a small-molecule OXTR agonist, inhibits alcohol intake in male, but not female, prairie voles socially housed in the presence of untreated cagemates. Taken together, results of this study support the promise of selectively targeting OXTR for individualized treatment of AUD.

Original languageEnglish (US)
Pages (from-to)920-928
Number of pages9
JournalNeuropsychopharmacology
Volume48
Issue number6
DOIs
StatePublished - May 2023

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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