ArticleBiological psychiatry2009
The delta(1) opioid receptor is a heterodimer that opposes the actions of the delta(2) receptor on alcohol intake.
Article in Biological psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Descriptive molecular pharmacology of the δ opioid receptor (DOR): A computational study with structural approach.PloS one · 2024Article
- Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.International journal of molecular sciences · 2022Review
- Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.Pharmacology, biochemistry, and behavior · 2022Article
- β-Arrestin-dependent ERK signaling reduces anxiety-like and conditioned fear-related behaviors in mice.Science signaling · 2021Article
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder.Frontiers in pharmacology · 2021Article
- Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.Journal of medicinal chemistry · 2020Article
- Behavioral, neurobiological, and neurochemical mechanisms of ethanol self-administration: A translational review.Pharmacology & therapeutics · 2020Review
- G protein-biased kratom-alkaloids and synthetic carfentanil-amide opioids as potential treatments for alcohol use disorder.British journal of pharmacology · 2020Article
- Arrestin recruitment and signaling by G protein-coupled receptor heteromers.Neuropharmacology · 2019Review
- A Review of the Therapeutic Potential of Recently Developed G Protein-Biased Kappa Agonists.Frontiers in pharmacology · 2019Review
- Usefulness of knockout mice to clarify the role of the opioid system in chronic pain.British journal of pharmacology · 2018Review
- Delta Opioid Pharmacology in Relation to Alcohol Behaviors.Handbook of experimental pharmacology · 2018Review
- Critical Role for GFrontiers in psychiatry · 2018Article
- Behavioral Characterization of β-Arrestin 1 Knockout Mice in Anxiety-Like and Alcohol Behaviors.Frontiers in behavioral neuroscience · 2018Article
- Two delta opioid receptor subtypes are functional in single ventral tegmental area neurons, and can interact with the mu opioid receptor.Neuropharmacology · 2017Article
- Identification of the First Marine-Derived Opioid Receptor "Balanced" Agonist with a Signaling Profile That Resembles the Endorphins.ACS chemical neuroscience · 2017Article
- The delta opioid receptor tool box.Neuroscience · 2016Review
- Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.Drug and alcohol dependence · 2016Article
- Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOpioid receptors are clinically important targets for both pain and alcohol abuse. Three opioid receptors have been cloned: mu, delta, and kappa, all of which effect alcohol consumption in animal models. Naltrexone is a nonselective opioid antagonist used for alcoholism, the clinical utility of which is limited by poor efficacy and adverse side effects. Here, we demonstrate that the therapeutic limitations of naltrexone may reflect its poor selectivity. Despite decades of research, several mysteries surround the pharmacology of these receptors. For example, two pharmacologically defined subtypes of delta receptors exist in vivo.
methodsEffects of delta subtype-selective ligands (naltrindole, naltriben, tan-67, 7-benzylidene naltrexone) were measured on ethanol consumption in C57BL/6 wildtype and opioid receptor knockout mice using a limited access two-bottle choice paradigm. Affinity and efficacy of naltriben, 7-benzylidenenaltrexone and tan-67 was measured in vitro using radioligand binding and Ca(2+)-mobilizationa assays.
resultsWe show that the subtypes of the delta receptor, delta(1) and delta(2), have opposing effects on ethanol consumption. We find that these effects are synergistic; thereby suggesting that delta(1) and delta(2) receptors are distinct molecular targets. Indeed, we provide both in vitro as well as in vivo evidence that the delta(1) subtype is a micro-delta heterodimer and that the delta(2) subtype is most likely a delta homomer.
conclusionsTogether these data provide insight into the limited actions of the clinically important drug naltrexone and identify a novel target with improved specificity and efficacy for the development of new therapeutics for the treatment of alcoholism.
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