ArticleThe Journal of pharmacology and experimental therapeutics2023
Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.
Article in The Journal of pharmacology and experimental therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Effects of opioids and stimulants on the respiratory system.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Fentanyl decreases arterial blood oxygen saturation more than furanylfentanyl in mice due to increased apnea.Psychopharmacology · 2026Article
- Oxytocin attenuates respiratory depression and reduces mortality from fentanyl and the combination of xylazine-fentanyl in rats.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Novel Swine Model of Respiratory Depression Induced by Fentanyl and Heroin Overdose.Research square · 2026Article
- Acute buprenorphine exposure depresses neonatal respiratory chemoreflexes in the presence or absence of naloxone.bioRxiv : the preprint server for biology · 2026Article
- Potentiation of fentanyl-induced respiratory depression by alcohol is not fully reversed by naloxone.JCI insight · 2026Article
- Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing.Research square · 2026Article
- The effects of fentanyl and dexmedetomidine on cardiorespiratory activity: implications for morbidity and mortality associated with adulterated fentanyl products.Frontiers in pharmacology · 2026Article
- Sex-related pharmacokinetic and pharmacological responses to 4F-furanylfentanyl.Frontiers in pharmacology · 2026Article
- Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach.Clinical pharmacokinetics · 2025Article
- Comparison of ventilatory depression by carfentanil, fentanyl, and heroin, and reversal by opioid receptor antagonists in rats.Neuropharmacology · 2025Article
- Roles of peripheral and central µAmerican journal of physiology. Lung cellular and molecular physiology · 2025Article
- Interactions between cardiorespiratory effects of fentanyl and xylazine and their reversal in male and female Sprague-Dawley rats.The Journal of pharmacology and experimental therapeutics · 2025Article
- Drug-specific recovery of long-term memory and visual discrimination after anaesthetic-induced unconsciousness in rats.British journal of anaesthesia · 2025Article
- Real world characteristics of central sleep apnea: a review of 29,000 consecutive patients undergoing polysomnography.Sleep & breathing = Schlaf & Atmung · 2025Article
- Proteomic analysis of plasma proteins during fentanyl withdrawal in ovariectomized female rats with and without estradiol.Journal of neuroendocrinology · 2025Article
- Reversal of morphine-induced respiratory depression with the µAmerican journal of physiology. Lung cellular and molecular physiology · 2025Article
- Xylazine exacerbates fentanyl-induced respiratory depression and bradycardia.The Journal of pharmacology and experimental therapeutics · 2025Article
- Synthetic cannabinoid receptor agonists exacerbate fentanyl-elicited respiratory depression and confer resistance to naloxone rescue in mice.Drug and alcohol dependence · 2025Article
- Searching for Synthetic Opioid Rescue Agents. 2: Identification of an Ultra-Potent Synthetic Opioid Rescue Agent.Journal of medicinal chemistry · 2025Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.