ArticleAlcoholism, clinical and experimental research2016
A Novel, Orally Bioavailable Nociceptin Receptor Antagonist, LY2940094, Reduces Ethanol Self-Administration and Ethanol Seeking in Animal Models.
Article in Alcoholism, clinical and experimental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Yohimbine as a pharmacological probe for alcohol research: a systematic review of rodent and human studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Pooled it
- Review
- Sex-Specific Relationships Between Nociceptin/Orphanin FQ Peptide (NOP) Receptors and Alcohol Drinking: Longitudinal PET Studies in Cynomolgus Monkeys.Basic & clinical pharmacology & toxicology · 2026Article
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.Cell reports · 2025Article
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- Emerging pharmacological targets for alcohol use disorder.Alcohol (Fayetteville, N.Y.) · 2024Review
- Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance.Psychopharmacology · 2024Article
- LY2940094, an NOPR antagonist, promotes oligodendrocyte generation and myelin recovery in an NOPR independent manner.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.Nature communications · 2024Article
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.bioRxiv : the preprint server for biology · 2024Article
- Pharmacological blockage of NOP receptors decreases ventral tegmental area dopamine neuronal activity through GABANeuropharmacology · 2024Article
- The life and times of endogenous opioid peptides: Updated understanding of synthesis, spatiotemporal dynamics, and the clinical impact in alcohol use disorder.Neuropharmacology · 2023Review
- Regulation of N-type calcium channels by nociceptin receptors and its possible role in neurological disorders.Molecular brain · 2022Review
- Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine-motivated behaviour.British journal of pharmacology · 2022Article
- Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.International journal of molecular sciences · 2021Review
- NOP receptor antagonism attenuates reinstatement of alcohol-seeking through modulation of the mesolimbic circuitry in male and female alcohol-preferring rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Review
- Genetically selected alcohol-preferring msP rats to study alcohol use disorder: Anything lost in translation?Neuropharmacology · 2021Review
- The Role of the Central Amygdala in Alcohol Dependence.Cold Spring Harbor perspectives in medicine · 2021Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe nociceptin/orphanin-FQ (or opioid receptor-like [ORL1]) receptor (NOP) is localized in the mesolimbic reward pathway and has been suggested to play a role in feeding, mood, stress, and addiction. Since its deorphanization in 1995, there has been a clear dichotomy in the literature regarding whether an agonist or antagonist would provide therapeutic benefit. Specifically, the literature reports indicate that NOP receptor antagonists produce efficacy in animal models of hyperphagia and antidepressant-like activity, whereas NOP agonists produce anxiolytic-like effects and dampen reward/addiction behaviors including ethanol consumption.
methodsWe characterize here the potent, orally bioavailable NOP antagonist, LY2940094, in rodent models of ethanol consumption, including ethanol self-administration, progressive ratio operant self-administration, stress-induced reinstatement of ethanol seeking, and in vivo microdialysis in the nucleus accumbens.
resultsLY2940094 dose dependently reduced homecage ethanol self-administration in Indiana alcohol-preferring (P) and Marchigian Sardinian alcohol-preferring (msP) rats, without affecting food/water intake or locomotor activity. Reduced ethanol intake in P rats did not show significant tolerance over 4 days of subchronic dosing. LY2940094 attenuated progressive ratio operant responding and break points for ethanol in P rats. Moreover, stress-induced reinstatement of ethanol seeking in msP rats was completely blocked by LY2940094. Furthermore, LY2940094 blocked ethanol-stimulated dopamine release in response to ethanol challenge (1.1 g/kg, intraperitoneally).
conclusionsOur findings demonstrate for the first time that blockade of NOP receptors attenuates ethanol self-administration and ethanol-motivated behaviors, stress-induced ethanol seeking, and ethanol-induced stimulation of brain reward pathways in lines of rats that exhibit excessive ethanol consumption. Results suggest that LY2940094 may have potential therapeutic utility in treating alcohol addiction.
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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.