ArticleScientific reports2016
Chronic Kappa opioid receptor activation modulates NR2B: Implication in treatment resistant depression.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 26 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 Prolongs the Antidepressant Effects of Ketamine in Adult Mice with Depression-like Behavior Induced by Adolescent Chronic Unpredictable Stress.International journal of molecular sciences · 2026Article
- C‑X‑C Motif Chemokine 10/C-X‑C Motif Chemokine Receptor 3 Signaling Induces Neural Senescence and Cognitive Impairments.ACS pharmacology & translational science · 2025Article
- Supraspinal kappa-opioid receptors: new therapeutic strategies for pain, pruritus, and negative emotions.Experimental brain research · 2025Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice.Chinese journal of integrative medicine · 2024Article
- Adverse Effects of Repeated, Intravenous Morphine on Recovery after Spinal Cord Injury in Young, Male Rats Are Blocked by a Kappa Opioid Receptor Antagonist.Journal of neurotrauma · 2022Article
- The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach.Handbook of experimental pharmacology · 2022Review
- The kappa opioid receptor antagonist aticaprant reverses behavioral effects from unpredictable chronic mild stress in male mice.Psychopharmacology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psychotomimetic and prodepressive effect by kappa opioid receptor (KOR) activation in rodents and human is widely known. Significantly, recent clinical investigations demonstrated the salutary effects of KOR antagonists in patients with treatment resistant depression, indicating essential role of KOR signaling in refractory depression. This study was undertaken to reveal the molecular determinant of KOR mediated depression and antidepressant response of KOR antagonist. We observed that chronic KOR activation by U50488, a selective KOR agonist, significantly increased depression like symptoms (behavioral despair, anhedonia and sociability) in C57BL/6J mice, which were blocked by KOR antagonist norBNI and antidepressant imipramine, but not by fluoxetine or citalopram. Further, chronic KOR activation increased phosphorylation of NR2B subunit of NMDA at tyrosine 1472 (pNR2B NMDA) in the hippocampus, but not in the cortex. Similar to behavioral effects norBNI and imipramine, but not SSRIs, blocked NR2B phosphorylation. Moreover, KOR induced depression like behaviors were reversed by NR2B selective inhibitor Ro 25-6981. Mechanistic studies in primary cultured neurons and brain tissues using genetic and pharmacological approaches revealed that stimulation of KOR modulates several molecular correlates of depression. Thus, these findings elucidate molecular mechanism of KOR signaling in treatment resistant depression like behaviors in mice.
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