ReviewNature neuroscience2014
Motivational activation: a unifying hypothesis of orexin/hypocretin function.
Review in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 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
205 citing papers in PubMed.
- Acute orexin antagonism selectively modulates anticipatory anxiety in humans: implications for addiction and anxiety.Translational psychiatry · 2022Trial
- Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study.The international journal of neuropsychopharmacology · 2021Trial
- First-in-human study with ACT-539313, a novel selective orexin-1 receptor antagonist.British journal of clinical pharmacology · 2020Trial
- The Relationship between Alcohol Craving and Insomnia Symptoms in Alcohol-Dependent Individuals.Alcohol and alcoholism (Oxford, Oxfordshire) · 2019Trial
- Trial
- Selective orexin receptor cross-over treatment increases resilience and expression of neuroplastic signaling genes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Review
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Mazindol Immediate-Release/Sustained-Release (IR/SR): A 50-Year Legacy of Multifaceted Mechanisms and Emerging Therapeutic Potential.Clinical drug investigation · 2026Review
- Prefrontal cortex-to-hypothalamic outputs orchestrate cue-potentiated palatable food consumption via AMPKβ2 signaling.Cell discovery · 2026Article
- Multisystem regulation of reward and addiction: beyond the dopaminergic system.Frontiers in pharmacology · 2026Review
- COAddiction biology · 2026Article
- Interoceptive Information of Physical Vigor Through Circulating Insulin-Like Growth Factor 1.FASEB bioAdvances · 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
- Implication of orexin transmission in chronic stress, hyperarousal, and neuroplasticity deficits: a mechanistic framework for depression and anxiety.Frontiers in psychiatry · 2026Review
- Activation of hypothalamic-pontine-spinal pathway promotes locomotor initiation and functional recovery after spinal cord injury in mice.Nature communications · 2025Article
- 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
- Article
- Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.Translational psychiatry · 2025Review
- Orexin and Lifestyle Habits: A Meaningful Connection Among Nutrition, Physical Activity, and Sleep Pattern in Health and Diseases.International journal of molecular sciences · 2025Review
145 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
5 authors.
Funding
Abstract
Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.
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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.