A review of the kappa opioid receptor system in opioid use.

Journal: Neuroscience and biobehavioral reviews

Volume: 162

Issue: 

Year of Publication: 

Affiliated Institutions:  Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT , USA. Department of Psychology, Southern Connecticut State University, New Haven, CT , USA. Islamic Azad University Tehran Medical Sciences School of Medicine, Iran. Pontifical Kavierian University, Bogotá, Colombia. University of Ghana Medical School, Accra, Ghana. Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT , USA. Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT , USA; Department of Psychiatry, Yale University School of Medicine,  George Street, Suite , New Haven, CT , USA; Department of Neurology, Yale University, New Haven, CT , USA. Department of Psychiatry, Yale University School of Medicine,  George Street, Suite , New Haven, CT , USA; Clinical Neuroscience Research Unit, Connecticut Mental Health Center,  Park Street, New Haven, CT , USA. Electronic address: gustavo.angarita@yale.edu.

Abstract summary 

The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids. A systematic scoping review was reported following PRISMA guidelines and conducted based on the published protocol. Comprehensive searches of several databases were done in the following databases: MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane. We included preclinical and clinical studies that tested the administration of KOR agonists/antagonists or dynorphin and/or measured dynorphin levels or KOR expression during opioid intoxication or withdrawal from opioids. One hundred studies were included in the final analysis. Preclinical administration of KOR agonists decreased drug-seeking/taking behaviors and opioid withdrawal symptoms. KOR antagonists showed mixed findings, depending on the agent and/or type of withdrawal symptom. Administration of dynorphins attenuated opioid withdrawal symptoms both in preclinical and clinical studies. In the limited number of available studies, dynorphin levels were found to increase in cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBL) of opioid use disorder subjects (OUD). In animals, dynorphin levels and/or KOR expression showed mixed findings during opioid use. The KOR/dynorphin system appears to have a multifaceted and complex nature rather than simply functioning as an anti-reward system. Future research in well-controlled study settings is necessary to better understand the clinical role of the KOR system in opioid use.

Authors & Co-authors:  Cayir Salih S Zhornitsky Simon S Barzegary Alireza A Sotomayor-Carreño Esteban E Sarfo-Ansah Wonder W Funaro Melissa C MC Matuskey David D Angarita Gustavo G

Study Outcome 

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Citations : 
Authors :  8
Identifiers
Doi : 10.1016/j.neubiorev.2024.105713
SSN : 1873-7528
Study Population
Male,Female
Mesh Terms
Other Terms
Dynorphins;Opioid use disorder;Opioids;κ-opioid receptor
Study Design
Study Approach
Country of Study
Publication Country
United States