ArticlePsychopharmacology2020
Modulation of cocaine-related behaviors by low doses of the potent KOR agonist nalfurafine in male C57BL6 mice.
Article in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Effects of repeated nalfurafine and VZTK35 treatments on fentanyl/cocaine mixture self-administration in a rat drug-vs.-food choice procedure.Psychopharmacology · 2026Article
- Large-scale reorganization of DNA methylation and upregulation of extracellular matrix genes in the dorsal dentate gyrus following cocaine taking.bioRxiv : the preprint server for biology · 2026Article
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder.Pharmacology, biochemistry, and behavior · 2025Review
- Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints.Neuroscience letters · 2025Article
- AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.Science advances · 2024Article
- Characterization of Pyrrolidinyl-hexahydro-pyranopiperazines as a Novel Kappa Opioid Receptor Agonist Scaffold.ACS chemical neuroscience · 2022Article
- An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.Pharmacological research · 2022Review
- Sex Differences in Kappa Opioid Receptor Agonist Mediated Attenuation of Chemotherapy-Induced Neuropathic Pain in Mice.Frontiers in pharmacology · 2022Article
- Preclinical Studies on Nalfurafine (TRK-820), a Clinically Used KOR Agonist.Handbook of experimental pharmacology · 2022Article
- Influences of Gender on Intravenous Nalbuphine Actions After Major Abdominal Surgery: A Multicenter Study.Pain and therapy · 2021Article
- Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.Future medicinal chemistry · 2021Article
- The kappa-opioid receptor agonist, nalfurafine, blocks acquisition of oxycodone self-administration and oxycodone's conditioned rewarding effects in male rats.Behavioural pharmacology · 2020Article
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
rationaleAgonists of the kappa opioid receptor (KOR) have been shown to block the rewarding effects of drugs of abuse, but with negative side effects. The antipruritic drug nalfurafine, approved in Japan in 2009, is a potent, selective KOR agonist that does not cause significant side effects in humans. Nalfurafine has not been extensively tested for its effect on drug reward and reinforcement in preclinical models.
objectivesThe goal of this study was to compare the effects of nalfurafine and a reference KOR agonist for a variety of KOR-mediated endpoints in male C57BL6 mice. Specifically, we aimed to evaluate the "therapeutic window"-doses of agonists lower than those eliciting negative side effects, while still effective for desired therapeutic effects.
methodsIn this study, several low doses of nalfurafine and U50,488 were tested for serum prolactin release, rotarod-mediated sedation, and place-conditioning in male C57BL6 mice. These agonists were also tested for effects on intravenous cocaine self-administration, both on an FR1 schedule and on a progressive ratio schedule for 0.5 mg/kg/infusion cocaine.
resultsSerum prolactin levels increased following doses of both nalfurafine (3 μg/kg and 10 μg/kg) and U50,488 (3 mg/kg). These doses did not cause sedation in the rotarod assay or aversion in a place-conditioning assay, but blocked conditioned place preference for cocaine. Immediate pretreatment of mice with 10 μg/kg nalfurafine and 3 mg/kg U50,488, however, potentiated cocaine self-administration. Further 10 μg/kg nalfurafine was also observed to potentiate cocaine-seeking behavior as demonstrated by increased progressive ratio break point.
conclusionsBoth nalfurafine and U50,488 showed a separation of negative side effects and the modulation of cocaine reward, suggesting this effect of KOR agonists at low doses may be characteristic of the KOR system in general. At higher doses, nalfurafine had similar effects to traditional KOR agonists like U50,488, indicating that its relative potency, rather than differences in KOR signaling, may be responsible for its unique effects in humans.
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