ArticlePharmacology, biochemistry, and behavior2021
Divergent profiles of fentanyl withdrawal and associated pain in mice and rats.
Article in Pharmacology, biochemistry, and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- A widespread internal brain state for fentanyl withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Projection-defined ventral tegmental area neurons exhibit fentanyl-induced molecular and functional adaptations that differentially support drug-context associations.bioRxiv : the preprint server for biology · 2025Article
- Eating a high fat/high carbohydrate diet enhances morphine tolerance, while eating a ketogenic diet mitigates morphine withdrawal in male rats.European journal of pharmacology · 2025Article
- Searching for Synthetic Opioid Rescue Agents. 2: Identification of an Ultra-Potent Synthetic Opioid Rescue Agent.Journal of medicinal chemistry · 2025Article
- Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl.Annual review of clinical psychology · 2025Review
- Benefits ofInternational journal of molecular sciences · 2025Article
- In vivo pharmacokinetic, pharmacodynamic and brain concentration comparison of fentanyl and para-fluorofentanyl in rats.Archives of toxicology · 2025Article
- Effects of xylazine on naloxone-precipitated fentanyl withdrawal in male and female rats.Drug and alcohol dependence · 2024Article
- Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Characterization and validation of a spontaneous acute and protracted oxycodone withdrawal model in male and female mice.Pharmacology, biochemistry, and behavior · 2024Article
- Article
- Nalbuphine Potentiates Reversal of Fentanyl Overdose by Naloxone.Pharmaceuticals (Basel, Switzerland) · 2024Article
- L-NAC and L-NAC methyl ester prevent and overcome physical dependence to fentanyl in male rats.Scientific reports · 2024Article
- Synaptic Structure and Transcriptomic Profiling of Reward and Sensory Brain Areas in Male Mice of Fentanyl Addiction.Substance abuse and rehabilitation · 2024Article
- The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement.Drug and alcohol dependence · 2023Article
- Liver Metabolomics and Inflammatory Profiles in Mouse Model of Fentanyl Overdose Treated with Beta-Lactams.Metabolites · 2023Article
- Advances in the characterization of negative affect caused by acute and protracted opioid withdrawal using animal models.Neuropharmacology · 2023Review
- Evidence for Endogenous Opioid Dependence Related to Latent Sensitization in a Rat Model of Chronic Inflammatory Pain.International journal of molecular sciences · 2023Article
- Effects of sub-lethal doses of fentanyl on vital physiologic functions and withdrawal-like behaviors in adult goats.Frontiers in physiology · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species' strengths as model systems and can inform experimental design in studies of opioid withdrawal.
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