ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission and conditioned place aversion.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 131 citations in OpenAlex.
- The Role of Kappa-Opioid Receptor/Dynorphin System in Modulating Neural-Circuits of Depression and Anxiety-A Review.Journal of cellular and molecular medicine · 2026Review
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Threonine-53 Phosphorylation of Dopamine Transporter Dictates κ-Opioid Receptor-Mediated Locomotor Suppression, Aversion, and Cocaine Reward.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.Journal of medicinal chemistry · 2024Article
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.Pharmacology, biochemistry, and behavior · 2024Article
- Dysregulation of kappa opioid receptor neuromodulation of lateral habenula synaptic function following a repetitive mild traumatic brain injury.Pharmacology, biochemistry, and behavior · 2024Article
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.Neuron · 2024Article
- Opioid modulation of prefrontal cortex cells and circuits.Neuropharmacology · 2024Review
- Co-targeting the kappa opioid receptor and dopamine transporter reduces motivation to self-administer cocaine and partially reverses dopamine system dysregulation.Scientific reports · 2024Article
- Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.bioRxiv : the preprint server for biology · 2024Article
- Opioidergic tuning of social attachment: reciprocal relationship between social deprivation and opioid abuse.Frontiers in neuroanatomy · 2024Review
- The claustrum-prelimbic cortex circuit through dynorphin/κ-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology.Nature communications · 2023Article
- Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner.Molecular psychiatry · 2023Article
- Sex Differences in Brain Region-Specific Activation of c-Fos following Kappa Opioid Receptor Stimulation or Acute Stress in Mice.International journal of molecular sciences · 2023Article
- The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects without Significant Effects on Locomotion, Food Reward, Learning and Memory, or Anxiety and Depressive-like Behaviors.Molecules (Basel, Switzerland) · 2023Article
- Pain-related cortico-limbic plasticity and opioid signaling.Neuropharmacology · 2023Review
- Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors.Brain sciences · 2023Review
- Recapitulating phenotypes of alcohol dependence via overexpression of Oprk1 in the ventral tegmental area of non-dependent TH::Cre rats.Neuropharmacology · 2023Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Kappa-opioid receptors (KORs) are important for motivation and other medial prefrontal cortex (mPFC)-dependent behaviors. Although KORs are present in the mPFC, their role in regulating transmission in this brain region and their contribution to KOR-mediated aversion are not known. Using in vivo microdialysis in rats and mice, we demonstrate that intra-mPFC administration of the selective KOR agonist U69,593 decreased local dopamine (DA) overflow, while reverse dialysis of the KOR antagonist nor-Binaltorphimine (nor-BNI) enhanced mPFC DA overflow. Extracellular amino-acid levels were also affected by KORs, as U69,593 reduced glutamate and GABA levels driven by the glutamate reuptake blocker, l-trans-pyrrolidine-2,4-dicarboxylate. Whole-cell recordings from mPFC layer V pyramidal neurons revealed that U69,593 decreased the frequency, but not amplitude, of glutamatergic mini EPSPs. To determine whether KOR regulation of mPFC DA overflow was mediated by KOR on DA terminals, we utilized a Cre recombinase-driven mouse line lacking KOR in DA neurons. In these mice, basal DA release or uptake was unaltered relative to controls, but attenuation of mPFC DA overflow by local U69,593 was not observed, indicating KOR acts directly on mPFC DA terminals to locally inhibit DA levels. Conditioning procedures were then used to determine whether mPFC KOR signaling was necessary for KOR-mediated aversion. U69,593-mediated conditioned place aversion was blocked by intra-mPFC nor-BNI microinjection. These findings demonstrate that mPFC KORs negatively regulate DA and amino-acid neurotransmission, and are necessary for KOR-mediated aversion.
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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.