Journal
ADDICTION BIOLOGY
Volume 26, Issue 3, Pages -Publisher
WILEY
DOI: 10.1111/adb.12946
Keywords
behavioral economics; demand; hypocretin; long access; opioids; reinstatement
Categories
Funding
- National Institute on Drug Abuse [K99DA045765, R01 DA006214]
- National Health and Medical Research Council of Australia C.J. Martin Fellowship [1072706]
- National Institutes of Health [K12 GM093854]
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The orexin system is critical in motivated drug taking, with IntA self-administration of fentanyl resulting in addiction-like behaviors reversed by orexin-1 receptor antagonist. The IntA model proves useful in studying opioid addiction.
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 1-h period (short access [ShA]), 6-h period (long access [LgA]), or IntA (5 min of access separated by 25 min of no access for 6 h) to fentanyl for 14 days. IntA produced a greater escalation of fentanyl intake, increased motivation for fentanyl on a behavioral economics task, persistent drug seeking during abstinence, and stronger cue-induced reinstatement compared with 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 neurons. Together, these 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.
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