ArticleThe Journal of physiology2013
Repeated in vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin/orexin-producing neurons in the lateral hypothalamus in mice.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Integration of cortical inputs in the lateral hypothalamus is dominated by the medial prefrontal cortex.The Journal of physiology · 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
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- The Role of Orexin Receptor Antagonists in Inhibiting Drug Addiction: A Review Article.Addiction & health · 2024Review
- Hypothalamic orexins as possible therapeutic agents in threat and spatial memory disorders.Frontiers in behavioral neuroscience · 2023Review
- Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.Biological psychiatry · 2022Review
- A Novel CaMKII Inhibitory Peptide Blocks Relapse to Morphine Seeking by Influencing Synaptic Plasticity in the Nucleus Accumbens Shell.Brain sciences · 2022Article
- From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.Endocrine reviews · 2022Review
- Arousal-Mediated Sleep Disturbance Persists During Cocaine Abstinence in Male Mice.Frontiers in neuroscience · 2022Article
- Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior.Molecular psychiatry · 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
- Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.The Journal of clinical investigation · 2020Article
- High-fat diet induces time-dependent synaptic plasticity of the lateral hypothalamus.Molecular metabolism · 2020Article
- Activation of lateral hypothalamic group III metabotropic glutamate receptors suppresses cocaine-seeking following abstinence and normalizes drug-associated increases in excitatory drive to orexin/hypocretin cells.Neuropharmacology · 2019Article
- Contribution of Dynorphin and Orexin Neuropeptide Systems to the Motivational Effects of Alcohol.Handbook of experimental pharmacology · 2018Article
- A Decade of Orexin/Hypocretin and Addiction: Where Are We Now?Current topics in behavioral neurosciences · 2017Review
- The dual orexin receptor antagonist TCS1102 does not affect reinstatement of nicotine-seeking.PloS one · 2017Article
- Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration.Journal of neurochemistry · 2015Article
- Orexin Signaling in the VTA Gates Morphine-Induced Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin-producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long-lasting, experience-dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine-conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up-regulation of AMPA-type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element-binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine-treated animals, suggesting that CREB-mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long-term potentiation (LTP) triggered by a high-frequency stimulation is facilitated in hypocretin neurons in cocaine-treated mice, suggesting that long-lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience-dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.
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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.