ArticleBrain research2017
Orexin/hypocretin-1 receptor antagonism reduces ethanol self-administration and reinstatement selectively in highly-motivated rats.
Article in Brain research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 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
67 citing papers in PubMed, 96 citations in OpenAlex.
- Functional interaction between orexin/CRF and orexin/dynorphin transmission in the infralimbic cortex modulates the stress-induced reinstatement of alcohol-seeking behavior in male and female Wistar rats.Neuropharmacology · 2026Article
- Article
- COAddiction biology · 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
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.Molecular psychiatry · 2025Article
- Stressed Avoider rats show blunted sensitivity to alcohol's aversive effects: Potential contributions of the lateral habenula and lateral hypothalamus.bioRxiv : the preprint server for biology · 2025Article
- Effects of daridorexant on rest/wake activity patterns and drinking in adult rats exposed to chronic ethanol vapor in adolescence.Alcohol (Fayetteville, N.Y.) · 2025Article
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- Functional interaction between orexin/dynorphin transmission in the posterior paraventricular nucleus of the thalamus following alcohol dependence: mediation of alcohol-seeking behavior.Frontiers in pharmacology · 2025Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- Pivotal role of orexin signaling in the posterior paraventricular nucleus of the thalamus during the stress-induced reinstatement of oxycodone-seeking behavior.Journal of psychopharmacology (Oxford, England) · 2024Article
- The dual orexin receptor antagonist suvorexant in alcohol use disorder and comorbid insomnia: A case report.Clinical case reports · 2024Article
- The Role of Orexin Receptor Antagonists in Inhibiting Drug Addiction: A Review Article.Addiction & health · 2024Review
- A novel, non-opioid, selective orexin-1 receptor antagonist for the treatment of substance use disorders.Neuroscience applied · 2024Article
- Dual orexin/hypocretin receptor antagonism attenuates NMDA receptor hypofunction-induced attentional impairments in a rat model of schizophrenia.Behavioural brain research · 2023Article
- Blockade of orexin receptors in the infralimbic cortex prevents stress-induced reinstatement of alcohol-seeking behaviour in alcohol-dependent rats.British journal of pharmacology · 2023Article
- A molecular network map of orexin-orexin receptor signaling system.Journal of cell communication and signaling · 2023Article
7 more citing papers are in PubMed but not listed here.
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 4 institutions in 2 countries.
Funding
Abstract
The orexin/hypocretin (ORX) system regulates motivation for natural rewards and drugs of abuse such as alcohol. ORX receptor antagonists, most commonly OX1R antagonists including SB-334867 (SB), decrease alcohol drinking, self-administration and reinstatement in both genetically-bred alcohol-preferring and outbred strains of rats. Importantly, levels of alcohol seeking and drinking in outbred rats are variable, as they are in humans. We have shown that OX1R antagonism selectively decreases homecage alcohol drinking in high-, but not low-alcohol-preferring rats. It is unknown, however, whether this effect is selective to homecage drinking or whether it also applies to alcohol seeking paradigms such as self-administration and reinstatement following extinction, in which motivation is high in the absence of alcohol. Here we trained Sprague Dawley rats to self-administer 20% ethanol paired with a light-tone cue on an FR3 regimen. Rats were then extinguished and subjected to cue-induced reinstatement. Rats were segregated into high- and low-ethanol-responding groups (HR and LR) based on self-administration levels. During self-administration and cue-induced reinstatement, rats were given SB or vehicle prior to ethanol seeking. In both conditions, OX1R antagonism decreased responding selectively in HR, but not LR rats. There were no non-specific effects of SB treatment on arousal or general behavior. These data indicate that ORX signaling at the OX1R receptor specifically regulates high levels of motivation for alcohol, even in the absence of direct alcohol reinforcement. This implicates the ORX system in the pathological motivation underlying alcohol abuse and alcoholism and demonstrates that the OX1R may be an important target for treating alcohol abuse.
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.