ArticleAddiction biology2021
Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.
Article in Addiction biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 82 citations in OpenAlex.
- Effects of suvorexant on diurnal cortisol and patient-reported stress during opioid withdrawal in a randomized trial.Psychoneuroendocrinology · 2025Trial
- Cued unpredictable intermittent access exacerbates loss of control over ethanol drinking.Neuropharmacology · 2026Article
- Can the incentive-sensitization theory of addiction incorporate addiction to opioid drugs?Psychopharmacology · 2026Review
- Cued unpredictable intermittent access exacerbates loss of control over ethanol drinking.bioRxiv : the preprint server for biology · 2026Article
- Marked sex differences are observed in heroin acquisition and affective states in rats but converge to similar levels of footshock stress-induced reinstatement.Psychopharmacology · 2026Article
- The relationship between duration of access to intravenous oxycodone self-administration, economic demand for oxycodone, and cognition in rats.Psychopharmacology · 2026Article
- Functional interaction between orexin/CRF and orexin/dynorphin transmission in the infralimbic cortex modulates the stress-induced reinstatement of alcohol-seeking behavior in male and female Wistar rats.Neuropharmacology · 2026Article
- A widespread internal brain state for fentanyl withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sleep regulates drug seeking and relapse - a perspective.Molecular psychiatry · 2026Review
- Preclinical abuse potential testing using behavioral economics and drug self-administration demand-curve analysis: A strategy to improve resolution of drug stratification for regulatory control.Pharmacological reviews · 2026Review
- Transcriptional response to chronic long-access fentanyl self-administration in rat habenula and amygdala.bioRxiv : the preprint server for biology · 2025Article
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.Translational psychiatry · 2025Review
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.Research square · 2025Article
- Behavioral economics of polysubstance use: The role of orexin-1 receptors in nicotine-induced augmentation of synthetic opioid consumption.Neuropharmacology · 2025Article
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.Molecular psychiatry · 2025Article
- Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice.Psychopharmacology · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
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 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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