ArticleAddiction biology2018
Hypocretin receptor 1 knockdown in the ventral tegmental area attenuates mesolimbic dopamine signaling and reduces motivation for cocaine.
Article in Addiction biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- 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
- Behavioral economics of polysubstance use: The role of orexin-1 receptors in nicotine-induced augmentation of synthetic opioid consumption.Neuropharmacology · 2025Article
- A Preliminary Report on the Effects of Daridorexant in Patients with Comorbid Insomnia and Substance Use Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Understanding zebrafish sleep and wakefulness physiology as an experimental model for biomedical research.Fish physiology and biochemistry · 2024Review
- Inactivation of ERK1/2 Signaling in Dopaminergic Neurons by Map Kinase Phosphatase MKP3 Regulates Dopamine Signaling and Motivation for Cocaine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine.Addiction neuroscience · 2023Article
- Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation.Neuroscience and biobehavioral reviews · 2023Review
- Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans.Pharmacology, biochemistry, and behavior · 2022Article
- Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone.Brain sciences · 2022Review
- Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Article
- Differential Roles of Intra-accumbal Orexin Receptors in Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference in the Rats.Neurochemical research · 2020Article
- Increased Number and Activity of a Lateral Subpopulation of Hypothalamic Orexin/Hypocretin Neurons Underlies the Expression of an Addicted State in Rats.Biological psychiatry · 2019Article
- Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits.Frontiers in psychiatry · 2019Review
- Recent advances in understanding the roles of hypocretin/orexin in arousal, affect, and motivation.F1000Research · 2018Review
- Parallels and Overlap: The Integration of Homeostatic Signals by Mesolimbic Dopamine Neurons.Frontiers in psychiatry · 2018Review
- Differential Aspects of Natural and Morphine Reward-related Behaviors in Conditioned Place Preference Paradigm.Basic and clinical neuroscienceArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The hypocretin receptor 1 (HCRTr1) is a critical participant in the regulation of motivated behavior. Previous observations demonstrate that acute pharmacological blockade of HCRTr1 disrupts dopamine (DA) signaling and the motivation for cocaine when delivered systemically or directly into the ventral tegmental area (VTA). To further examine the involvement of HCRTr1 in regulating reward and reinforcement processing, we employed an adeno-associated virus to express a short hairpin RNA designed to knock down HCRTr1. We injected virus into the VTA and examined the effects of HCRTr1 knockdown on cocaine self-administration and DA signaling in the nucleus accumbens (NAc) core. We determined that the viral approach was effective at reducing HCRTr1 expression without affecting the expression of hypocretin receptor 2 or DA-related mRNAs. We next examined the effects of HCRTr1 knockdown on cocaine self-administration, observing delayed acquisition under a fixed-ratio schedule and reduced motivation for cocaine under a progressive ratio schedule. These effects did not appear to be associated with alterations in sleep/wake activity. Using fast-scan cyclic voltammetry, we then examined whether HCRTr1 knockdown alters DA signaling dynamics in the NAc core. We observed reduced DA release and slower uptake rate as well as attenuated cocaine-induced DA uptake inhibition in rats with knockdown of HCRTr1. These observations indicate that HCRTr1 within the VTA influence the motivation for cocaine, likely via alterations in DA signaling in the NAc.
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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.