ArticleBrain research2016
The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.
Article in Brain research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Acute orexin antagonism selectively modulates anticipatory anxiety in humans: implications for addiction and anxiety.Translational psychiatry · 2022Trial
- Review
- Sex-Specific Effects of Hypocretin Receptor Signaling in Corticotropin-Releasing Factor Neurons on Alcohol Drinking, Anxiety, and Extended Amygdala Neuronal Excitability.Biological psychiatry global open science · 2026Article
- Behavioral profile predicts ethanol preference in adolescent mice, but not in adults: A machine learning approach.Alcohol, clinical & experimental research · 2026Article
- Modulatory effects of orexin and dynorphin on stress-related alcohol seeking and relapse: pivotal role of the posterior paraventricular nucleus of the thalamus.Frontiers in pharmacology · 2026Review
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Orexin receptors: possible therapeutic targets for psychiatric disorders.Psychopharmacology · 2025Review
- Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit/Stress Surfeit Disorder.Current topics in behavioral neurosciences · 2025Review
- The Role of Orexin Receptor Antagonists in Inhibiting Drug Addiction: A Review Article.Addiction & health · 2024Review
- Orexinergic lateral hypothalamus (LH) projections to medial septum (MS) modulate ethanol-induced sedation in male and female mice and binge-like ethanol drinking in male mice only.Alcohol (Fayetteville, N.Y.) · 2024Article
- Effects of single and dual hypocretin-receptor blockade or knockdown of hypocretin projections to the central amygdala on alcohol drinking in dependent male rats.Addiction neuroscience · 2022Article
- Exploring the Therapeutic Potential of Targeting Purinergic and Orexinergic Receptors in Alcoholic Neuropathy.Neurotoxicity research · 2022Review
- Alternative use of suvorexant (BelsomraFrontiers in behavioral neuroscience · 2022Article
- Circuit selectivity in drug versus natural reward seeking behaviors.Journal of neurochemistry · 2021Review
- Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.Addiction biology · 2021Article
- Recent Perspectives on Sex Differences in Compulsion-Like and Binge Alcohol Drinking.International journal of molecular sciences · 2021Review
- Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking.Scientific reports · 2021Article
- Understanding the Role of Orexin Neuropeptides in Drug Addiction: Preclinical Studies and Translational Value.Frontiers in behavioral neuroscience · 2021Review
- Drug addiction co-morbidity with alcohol: Neurobiological insights.International review of neurobiology · 2021Review
- Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.Pharmacological reviews · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated.
Indexed as
Identifiers
What OpenQuestion holds
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.