ArticleBiological psychiatry2019
Increased Number and Activity of a Lateral Subpopulation of Hypothalamic Orexin/Hypocretin Neurons Underlies the Expression of an Addicted State in Rats.
Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Circadian Influences on the Habenula and Their Potential Contribution to Neuropsychiatric Disorders.Frontiers in behavioral neuroscience · 2021Pooled it
- The Effect of Digital Addiction Training on University Students' Digital Addiction, Sleep Quality, and Orexin-A Levels: Randomized Controlled Trial.BMC psychology · 2025Trial
- The Relationship between Alcohol Craving and Insomnia Symptoms in Alcohol-Dependent Individuals.Alcohol and alcoholism (Oxford, Oxfordshire) · 2019Trial
- Cued unpredictable intermittent access exacerbates loss of control over ethanol drinking.Neuropharmacology · 2026Article
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- Cued unpredictable intermittent access exacerbates loss of control over ethanol drinking.bioRxiv : the preprint server for biology · 2026Article
- Selective orexin receptor cross-over treatment increases resilience and expression of neuroplastic signaling genes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Methamphetamine potentiates the use of outcome-specific associations via a hypothalamic-dopamine circuit.Neuron · 2026Article
- 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
- Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sleep regulates drug seeking and relapse - a perspective.Molecular psychiatry · 2026Review
- 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
- Preclinical abuse potential testing using behavioral economics and drug self-administration demand-curve analysis: A strategy to improve resolution of drug stratification for regulatory control.Pharmacological reviews · 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
- Hypocretin signaling in the central amygdala drives methamphetamine self-administration in male rats.Neuropharmacology · 2025Article
- Found in translation: orexin receptor antagonism for the treatment of opioid use disorder.Translational psychiatry · 2025Review
- 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
- Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats.Addiction neuroscience · 2025Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe orexin (hypocretin) system is important for reward-driven motivation but has not been implicated in the expression of a multiphenotype addicted state.
methodsRats were assessed for economic demand for cocaine before and after 14 days of short access, long access, or intermittent access (IntA) to cocaine. Rats were also assessed for a number of other DSM-5-relevant addiction criteria following differential access conditions. Orexin system function was assessed by quantification of numbers and activity of orexin cells, pharmacological blockade of the orexin-1 receptor, and subregion-specific knockdown of orexin cell populations.
resultsIntA produced a cluster of addiction-like behaviors that closely recapitulate key diagnostic criteria for addiction to a greater extent than long access or short access. IntA was accompanied by an increase in number and activity of orexin-expressing neurons within the lateral hypothalamic subregion. This increase in orexin cell number and activity persisted during protracted withdrawal from cocaine for at least 150 days and was accompanied by enhanced incubation of craving in the same rats. Selective knockdown of lateral hypothalamic orexin neurons reduced motivation for cocaine, and orexin-1 receptor signaling played a larger role in drug seeking after IntA.
conclusionsWe provide the first evidence that lateral hypothalamic orexin system function extends beyond general reward seeking to play a critical role in expression of a multiphenotype addiction-like state. Thus, the orexin system is a potential novel target for pharmacotherapies designed to treat cocaine addiction. In addition, these data point to the IntA model as a preferred approach to modeling addiction-like behavior in rats.
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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.