ArticleThe Journal of pharmacology and experimental therapeutics2015
Effects of μ-opioid receptor agonists in assays of acute pain-stimulated and pain-depressed behavior in male rats: role of μ-agonist efficacy and noxious stimulus intensity.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- DPsychopharmacology · 2025Article
- NOP agonist AT-403 promoted sleep in lactic acid-induced acute pain model.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice.The Journal of pharmacology and experimental therapeutics · 2024Article
- Article
- Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death.NeuroImmune pharmacology and therapeutics · 2023Article
- Climbing behavior by mice as an endpoint for preclinical assessment of drug effects in the absence and presence of pain.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Role of mu opioid receptor (MOR) agonist efficacy as a determinant of opioid antinociception in a novel assay of pain-depressed behavior in female and male mice.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats.Psychopharmacology · 2022Article
- Lack of effect of different pain-related manipulations on opioid self-administration, reinstatement of opioid seeking, and opioid choice in rats.Psychopharmacology · 2021Article
- Effects of Ketoprofen and Morphine on Pain-Related Depression of Nestlet Shredding in Male and Female Mice.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- Factors mediating pain-related risk for opioid use disorder.Neuropharmacology · 2021Review
- Effects of repeated treatment with monoamine-transporter-inhibitor antidepressants on pain-related depression of intracranial self-stimulation in rats.Psychopharmacology · 2020Article
- Interactions between pain states and opioid reward assessed with intracranial self-stimulation in rats.Neuropharmacology · 2019Review
- Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment.Neuroscience and biobehavioral reviews · 2019Review
- Effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 on pain-depressed behavior in rats: comparison with ketorolac and diazepam.Behavioural pharmacology · 2019Article
- Core Outcome Measures in Preclinical Assessment of Candidate Analgesics.Pharmacological reviews · 2019Review
- Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.The Journal of clinical investigation · 2019Article
- Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.Psychopharmacology · 2018Article
- Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors.Experimental and therapeutic medicine · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Pain is associated with stimulation of some behaviors and depression of others, and μ-opioid receptor agonists are among the most widely used analgesics. This study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six μ-agonists that varied in efficacy at μ-opioid receptors (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine). Intraperitoneal injection of diluted lactic acid served as an acute noxious stimulus to either stimulate stretching or depress operant responding maintained by electrical stimulation in an intracranial self-stimulation (ICSS). All μ-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists methadone and fentanyl were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. All μ-agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy μ-agonist nalbuphine, but not the high-efficacy μ-agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective μ-opioid analgesics and reveal distinctions between opioids based on efficacy at the μ-receptor. These results also support the use of parallel assays of pain-stimulated and -depressed behaviors to evaluate analgesic efficacy of candidate drugs.
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Registered trials
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.