ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents, Monitored In Vivo with PET.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Imaging Kappa Opioid Receptors in the Living Brain with Positron Emission Tomography.Handbook of experimental pharmacology · 2022Review
- Synthesis and Pharmacological Evaluation of Fluorinated Quinoxaline-Based κ-Opioid Receptor (KOR) Agonists Designed for PET Studies.ChemMedChem · 2020Article
- Salvinorin A Does Not Affect Seizure Threshold in Mice.Molecules (Basel, Switzerland) · 2020Article
- Role of Nuclear Imaging to Understand the Neural Substrates of Brain Disorders in Laboratory Animals: Current Status and Future Prospects.Frontiers in behavioral neuroscience · 2020Review
- A Survey of Molecular Imaging of Opioid Receptors.Molecules (Basel, Switzerland) · 2019Review
- Is There a Role for GPCR Agonist Radiotracers in PET Neuroimaging?Frontiers in molecular neuroscience · 2019Review
- Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders.Frontiers in psychiatry · 2019Review
- Kappa opioid receptor binding in major depression: A pilot study.Synapse (New York, N.Y.) · 2018Article
- PET Neurochemical Imaging Modes.Seminars in nuclear medicine · 2016Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Monitoring changes in opioid receptor binding with positron emission tomography (PET) could lead to a better understanding of tolerance and addiction because altered opioid receptor dynamics following agonist exposure has been linked to tolerance mechanisms. We have studied changes in kappa opioid receptor (KOR) binding availability in vivo with PET following kappa opioid agonist administration. Male Sprague-Dawley rats (n=31) were anesthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administration of the KOR selective radiotracer [(11)C]GR103545. When salvinorin A was administered 1 min prior to injection of the radiotracer, [(11)C]GR103545 binding potential (BPND) was decreased in a dose-dependent manner, indicating receptor binding competition. In addition, the unique pharmacokinetics of salvinorin A (half-life ~8 min in non-human primates) allowed us to study the residual impact on KOR after the drug had eliminated from the brain. Salvinorin A was administered up to 5 h prior to [(11)C]GR103545, and the changes in BPND were compared with baseline, 2.5 h, 1 h, and 1 min pretreatment times. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40-49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET.
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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.