ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
NOP receptor antagonism attenuates reinstatement of alcohol-seeking through modulation of the mesolimbic circuitry in male and female alcohol-preferring rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 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
- Sex-Specific Relationships Between Nociceptin/Orphanin FQ Peptide (NOP) Receptors and Alcohol Drinking: Longitudinal PET Studies in Cynomolgus Monkeys.Basic & clinical pharmacology & toxicology · 2026Article
- Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system.Cell reports · 2025Article
- Identification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder.Nature. Mental health · 2025Article
- 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
- Pharmacological blockage of NOP receptors decreases ventral tegmental area dopamine neuronal activity through GABANeuropharmacology · 2024Article
- Rostromedial tegmental nucleus nociceptin/orphanin FQ (N/OFQ) signaling regulates anxiety- and depression-like behaviors in alcohol withdrawn rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- 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
- Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways.Psychopharmacology · 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
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9 authors at 2 institutions in 2 countries.
Funding
Abstract
In patients suffering from alcohol use disorder (AUD), stress and environmental stimuli associated with alcohol availability are important triggers of relapse. Activation of the nociceptin opioid peptide (NOP) receptor by its endogenous ligand Nociceptin/Orphanin FQ (N/OFQ) attenuates alcohol drinking and relapse in rodents, suggesting that NOP agonists may be efficacious in treating AUD. Intriguingly, recent data demonstrated that also blockade of NOP receptor reduced alcohol drinking in rodents. To explore further the potential of NOP antagonism, we investigated its effects on the reinstatement of alcohol-seeking elicited by administration of the α2 antagonist yohimbine (1.25 mg/kg, i.p.) or by environmental conditioning factors in male and female genetically selected alcohol-preferring Marchigian Sardinian (msP) rats. The selective NOP receptor antagonist LY2817412 (0.0, 3.0, 10.0, and 30.0 mg/kg) was first tested following oral (p.o.) administration. We then investigated the effects of LY2817412 (1.0, 3.0, 6.0 μg/μl/rat) microinjected into three candidate mesolimbic brain regions: the ventral tegmental area (VTA), the central nucleus of the amygdala (CeA), and the nucleus accumbens (NAc). We found that relapse to alcohol seeking was generally stronger in female than in male rats and oral administration of LY2817412 reduced yohimbine- and cue-induced reinstatement in both sexes. Following site-specific microinjections, LY2817412 reduced yohimbine-induced reinstatement of alcohol-seeking when administered into the VTA and the CeA, but not in the NAc. Cue-induced reinstatement was suppressed only when LY2817412 was microinjected into the VTA. Infusions of LY2817412 into the VTA and the CeA did not alter saccharin self-administration. These results demonstrate that NOP receptor blockade prevents the reinstatement of alcohol-seeking through modulation of mesolimbic system circuitry, providing further evidence of the therapeutic potential of NOP receptor antagonism in AUD.
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