ReviewBiological psychiatry2022
Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.
Review in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.Translational psychiatry · 2026Pooled it
- Orexin receptor antagonists in the treatment of insomnia associated with psychiatric disorders: a systematic review.Translational psychiatry · 2024Pooled it
- Dysregulated eating behaviour and microbiota-based interventions targeting eating disorders and food addiction.Gut microbes · 2026Review
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- Outcompeting opioid-induced respiratory depression.Journal of thoracic disease · 2026Article
- Social defeat stress responses in the stress alternative model are dependent on sex and anterior basolateral amygdala orexin 2 receptors.Biology of sex differences · 2026Article
- 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
- Multisystem regulation of reward and addiction: beyond the dopaminergic system.Frontiers in pharmacology · 2026Review
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The Concise Guide to PHARMACOLOGY 2025/26: G protein-coupled receptors.British journal of pharmacology · 2025Review
- Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.Translational psychiatry · 2025Review
- The effects of nicotine on sleep in female C57BL/6J mice.Behavioural brain research · 2025Article
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.Research square · 2025Article
- 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
- A Preliminary Report on the Effects of Daridorexant in Patients with Comorbid Insomnia and Substance Use Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- Sleep Loss and Substance Use Disorders: An Issue from Adolescents to Adults.Behavioral sciences (Basel, Switzerland) · 2025Review
- Case Report: REM sleep without atonia in an adult with pediatric acute-onset neuropsychiatric syndrome: a case study and mechanistic insights.Frontiers in sleep · 2025Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In 2014, we proposed that orexin signaling transformed motivationally relevant states into adaptive behavior directed toward exploiting an opportunity or managing a threat, a process we referred to as motivational activation. Advancements in animal models since then have permitted higher-resolution measurements of motivational states; in particular, the behavioral economics approach for studying drug demand characterizes conditions that lead to the enhanced motivation that underlies addiction. This motivational plasticity is paralleled by persistently increased orexin expression in a topographically specific manner-a finding confirmed across species, including in humans. Normalization of orexin levels also reduces drug motivation in addiction models. These new advancements lead us to update our proposed framework for the orexin function. We now propose that the capacity of orexin neurons to exhibit dynamic shifts in peptide production contributes to their role in adaptive motivational regulation and that this is achieved via a pool of reserve orexin neurons. This reserve is normally bidirectionally recruited to permit motivational plasticity that promotes flexible, adaptive behavior. In pathological states such as addiction, however, we propose that the orexin system loses capacity to adaptively adjust peptide production, resulting in focused hypermotivation for drug, driven by aberrantly and persistently high expression in the orexin reserve pool. This mechanistic framework has implications for the understanding and treatment of several psychiatric disorders beyond addiction, particularly those characterized by motivational dysfunction.
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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.