Apr 25, 2020

Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.

BioRxiv : the Preprint Server for Biology
J. E. FragaleGary Aston-Jones

Abstract

The orexin (hypocretin) system plays a critical role in motivated drug-taking. Cocaine self-administration with the intermittent access (IntA) procedure produces a robust addiction-like state that is orexin-dependent. Here, we sought to determine the role of the orexin system in opioid addiction using IntA self-administration of fentanyl. Different groups of male rats were either given continuous access in 1h (short access; ShA), or 6h periods (long access, LgA), or IntA (5min of access separated by 25min of no-access) to fentanyl for 14 days. IntA produced a greater escalation of fentanyl intake, motivation for fentanyl on a behavioral economics task, persistent drug seeking during abstinence, and cued-induced reinstatement compared to rats given ShA or LgA. We found that addiction behaviors induced by IntA to fentanyl were reversed by the orexin-1 receptor antagonist SB-334867. IntA to fentanyl was also associated with a persistent increase in the number of orexin-expressing neurons. Together, results indicate that the IntA model is a useful tool in the study of opioid addiction, and that the orexin system is critical for the maintenance of addiction behaviors induced by IntA self-administration of fentanyl.

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Vertebrates
Genes
Regulation of Biological Process
Yeasts
Poecilia formosa
Clone
Zebrafish
Kin protein, rat
Clonopsis sp. clonal androgen 1
Species

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.