TY - JOUR
T1 - Male-selective effects of oxytocin agonism on alcohol intake
T2 - behavioral assessment in socially housed prairie voles and involvement of RAGE
AU - Potretzke, Sheena
AU - Zhang, Yangmiao
AU - Li, Ju
AU - Fecteau, Kristopher M.
AU - Erikson, David
AU - Hibert, Marcel
AU - Ryabinin, Andrey E.
N1 - Funding Information:
Research reported in this publication was supported by the National Institutes of Health (NIH) award numbers F31AA028669, R01AA019793, R01AA028680 and S10OD026701. The Endocrine Technologies Core (ETC) is supported (in part) by NIH grant P51 OD011092 for operation of the Oregon National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
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U2 - 10.1038/s41386-022-01490-3
DO - 10.1038/s41386-022-01490-3
M3 - Article
AN - SCOPUS:85141733364
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -