ArticleACS chemical neuroscience2015
Hypocretin/Orexin regulation of dopamine signaling and cocaine self-administration is mediated predominantly by hypocretin receptor 1.
Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- Selective orexin receptor cross-over treatment increases resilience and expression of neuroplastic signaling genes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sleep regulates drug seeking and relapse - a perspective.Molecular psychiatry · 2026Review
- 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
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Review
- The Role of Orexin Receptor Antagonists in Inhibiting Drug Addiction: A Review Article.Addiction & health · 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
- A novel, non-opioid, selective orexin-1 receptor antagonist for the treatment of substance use disorders.Neuroscience applied · 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
- Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.Neurochemical research · 2023Review
- Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation.Neuroscience and biobehavioral reviews · 2023Review
- Sleep-mediated regulation of reward circuits: implications in substance use disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans.Pharmacology, biochemistry, and behavior · 2022Article
- Effects of single and dual hypocretin-receptor blockade or knockdown of hypocretin projections to the central amygdala on alcohol drinking in dependent male rats.Addiction neuroscience · 2022Article
- Article
- The Effect of Orexin-2 and Endocannabinoid-1 Antagonists on Neuronal Activity of Hippocampal CA1 Pyramidal Neurons in Response to Tramadol in Rats.Advanced biomedical research · 2022Article
- Sleep dysregulation in binge eating disorder and "food addiction": the orexin (hypocretin) system as a potential neurobiological link.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Review
- 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
- Interaction between cocaine use and sleep behavior: A comprehensive review of cocaine's disrupting influence on sleep behavior and sleep disruptions influence on reward seeking.Pharmacology, biochemistry, and behavior · 2021Review
- Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Extensive evidence suggests that the hypocretins/orexins influence cocaine reinforcement and dopamine signaling via actions at hypocretin receptor 1. By comparison, the involvement of hypocretin receptor 2 in reward and reinforcement processes has received relatively little attention. Thus, although there is some evidence that hypocretin receptor 2 regulates intake of some drugs of abuse, it is currently unclear to what extent hypocretin receptor 2 participates in the regulation of dopamine signaling or cocaine self-administration, particularly under high effort conditions. To address this, we examined the effects of hypocretin receptor 1, and/or hypocretin receptor 2 blockade on dopamine signaling and cocaine reinforcement. We used in vivo fast scan cyclic voltammetry to test the effects of hypocretin antagonists on dopamine signaling in the nucleus accumbens core and a progressive ratio schedule to examine the effects of these antagonists on cocaine self-administration. Results demonstrate that blockade of either hypocretin receptor 1 or both hypocretin receptor 1 and 2 significantly reduces the effects of cocaine on dopamine signaling and decreases the motivation to take cocaine. In contrast, blockade of hypocretin receptor 2 alone had no significant effects on dopamine signaling or self-administration. These findings suggest a differential involvement of the two hypocretin receptors, with hypocretin receptor 1 appearing to be more involved than hypocretin receptor 2 in the regulation of dopamine signaling and cocaine self-administration. When considered with the existing literature, these data support the hypothesis that hypocretins exert a permissive influence on dopamine signaling and motivated behavior via preferential actions on hypocretin receptor 1.
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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.