ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 104 citations in OpenAlex.
- Review
- Neural Circuit Connections and Functions of Locus Coeruleus-Norepinephrine System.International journal of molecular sciences · 2025Review
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- Nalfurafine reverses fentanyl-induced muscle rigidity and respiratory depression without affecting sedation in rats: decoupling respiration from sedation.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Peripheral CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024Review
- Properties and modulation of excitatory inputs to the locus coeruleus.The Journal of physiology · 2022Article
- Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking.Neurobiology of stress · 2021Review
- The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal.The European journal of neuroscience · 2020Review
- The role of co-neurotransmitters in sleep and wake regulation.Molecular psychiatry · 2019Review
- The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.Neuron · 2019Article
- Active control of arousal by a locus coeruleus GABAergic circuit.Nature neuroscience · 2019Article
- Reduced Sensory-Evoked Locus Coeruleus-Norepinephrine Neural Activity in Female Rats With a History of Dietary-Induced Binge Eating.Frontiers in psychology · 2019Article
- Untangling the complexity of opioid receptor function.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Review
- Anti-stress neuropharmacological mechanisms and targets for addiction treatment: A translational framework.Neurobiology of stress · 2018Review
- Kappa opioid receptor binding in major depression: A pilot study.Synapse (New York, N.Y.) · 2018Article
- Persistent Stress-Induced Neuroplastic Changes in the Locus Coeruleus/Norepinephrine System.Neural plasticity · 2018Review
- Contribution of Dynorphin and Orexin Neuropeptide Systems to the Motivational Effects of Alcohol.Handbook of experimental pharmacology · 2018Article
- Expression of protein kinase A and the kappa opioid receptor in selected brain regions and conditioned place aversion in morphine-dependent rats.Oncotarget · 2017Article
- Co-localization of the cannabinoid type 1 receptor with corticotropin-releasing factor-containing afferents in the noradrenergic nucleus locus coeruleus: implications for the cognitive limb of the stress response.Brain structure & function · 2017Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.
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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.