Intravenous fentanyl self-administration in male and female C57BL/6J and DBA/2J mice

The genetic mechanisms underlying fentanyl addiction, a highly heritable disease, are unknown. Identifying these mechanisms will lead to better risk assessment, early diagnosis, and improved intervention. To this end, we used intravenous fentanyl self-administration to quantify classical self-admini...

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Bibliographic Details
Published in:Scientific reports 2023-01, Vol.13 (1), p.799-12, Article 799
Main Authors: Leonardo, Michael, Brunty, Sarah, Huffman, Jessica, Kastigar, Alexis, Dickson, Price E.
Format: Article
Language:English
Subjects:
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Addictions
Animals
Female
Fentanyl
Humanities and Social Sciences
Inbreeding
Intravenous administration
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Motor Activity - physiology
multidisciplinary
Phenotype
Phenotypes
Reinstatement
Risk assessment
Science
Science (multidisciplinary)
Self-administration
Sexual behavior
Species Specificity
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Summary:The genetic mechanisms underlying fentanyl addiction, a highly heritable disease, are unknown. Identifying these mechanisms will lead to better risk assessment, early diagnosis, and improved intervention. To this end, we used intravenous fentanyl self-administration to quantify classical self-administration phenotypes and addiction-like fentanyl seeking in male and female mice from the two founder strains of the BXD recombinant inbred mouse panel (C57BL/6J and DBA/2J). We reached three primary conclusions from these experiments. First, mice from all groups rapidly acquired intravenous fentanyl self-administration and exhibited a dose–response curve, extinction burst, and extinction of the learned self-administration response. Second, fentanyl intake (during acquisition and dose response) and fentanyl seeking (during extinction) were equivalent among groups. Third, strain effects, sex effects, or both were identified for several addiction-like behaviors (cue-induced reinstatement, stress-induced reinstatement, escalation of intravenous fentanyl self-administration). Collectively, these data indicate that C57BL/6J and DBA/2J mice of both sexes were able to acquire, regulate, and extinguish intravenous fentanyl self-administration. Moreover, these data reveal novel strain and sex effects on addiction-like behaviors in the context of intravenous fentanyl self-administration in mice and indicate that the full BXD panel can be used to identify and dissect the genetic mechanisms underlying these effects.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-27992-8