ArticleFrontiers in neuroscience2016
Nucleus Accumbens Shell and mPFC but Not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking.
Article in Frontiers in neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- 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
- Effects of daridorexant on rest/wake activity patterns and drinking in adult rats exposed to chronic ethanol vapor in adolescence.Alcohol (Fayetteville, N.Y.) · 2025Observational
- Function of orexin-1 receptor signaling in the olfactory tubercle in odor-guided attraction and aversion.Communications biology · 2024Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation.International journal of molecular sciences · 2024Review
- Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.Biological psychiatry · 2022Review
- Actions of feeding-related peptides on the mesolimbic dopamine system in regulation of natural and drug rewards.Addiction neuroscience · 2022Article
- Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.Brain sciences · 2022Review
- Alternative use of suvorexant (BelsomraFrontiers in behavioral neuroscience · 2022Article
- Recent Perspectives on Sex Differences in Compulsion-Like and Binge Alcohol Drinking.International journal of molecular sciences · 2021Review
- The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse.Neuropharmacology · 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
- Nucleus accumbens shell Orexin-1 receptors are not needed for single-bottle limited daily access alcohol intake in C57BL/6 mice.Alcohol (Fayetteville, N.Y.) · 2020Article
- Differential Roles of Intra-accumbal Orexin Receptors in Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rats.Neurochemical research · 2020Article
- The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task.Brain research · 2020Article
- Blockade of Orexin Receptors in the Posterior Paraventricular Nucleus of the Thalamus Prevents Stress-Induced Reinstatement of Reward-Seeking Behavior in Rats With a History of Ethanol Dependence.Frontiers in integrative neuroscience · 2020Article
- A novel NMDA receptor-based intervention to suppress compulsion-like alcohol drinking.Neuropharmacology · 2019Article
- Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future.Neuroscience and biobehavioral reviews · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle. Inhibition of OX1Rs with the widely used SB-334867 within the medial NAc Shell (mNAsh) significantly reduced drinking of alcohol, with no effect on saccharin intake, and no effect on alcohol consumption when infused above the mNAsh. In contrast, intra-mNAsh infusion of the orexin-2 receptor TCS-OX2-29 had no impact on alcohol drinking. In addition, OX1R inhibition within the aINS had no effect on excessive drinking, which was surprising given the importance of aINS-NAc circuits in promoting alcohol consumption and the role for aINS OX1Rs in driving nicotine intake. However, OX1R inhibition within the mPFC did reduce alcohol drinking, indicating cortical OXR involvement in promoting intake. Also, in support of the critical role for mNAsh OX1Rs, SB within the mNAsh also significantly reduced operant alcohol self-administration in rats. Finally, orexin ex vivo enhanced firing in mNAsh neurons from alcohol-drinking mice, with no effect on evoked EPSCs or input resistance; a similar orexin increase in firing without a change in input resistance was observed in alcohol-naïve mice. Taken together, our results suggest that OX1Rs within the mNAsh and mPFC, but not the aINS, play a central role in driving excessive alcohol drinking.
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Registered trials
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