The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence

Biological Psychiatry
Samuel David Clark, Anissa Abi-Dargham

Abstract

Schizophrenia is a debilitating mental illness that affects approximately 1% of the world's population. Despite much research in its neurobiology to aid in developing new treatments, little progress has been made. One system that has not received adequate attention is the kappa opioid system and its potential role in the emergence of symptoms, as well as its therapeutic potential. Here we present an overview of the kappa system and review various lines of evidence derived from clinical studies for dynorphin and kappa opioid receptor involvement in the pathology of both the positive and negative symptoms of schizophrenia. This overview includes evidence for the psychotomimetic effects of kappa opioid receptor agonists in healthy volunteers and their reversal by the pan-opioid antagonists naloxone and naltrexone and evidence for a therapeutic benefit in schizophrenia for 4 pan-opioid antagonists. We describe the interactions between kappa opioid receptors and the dopaminergic pathways that are disrupted in schizophrenia and the histologic evidence suggesting abnormal kappa opioid receptor signaling in schizophrenia. We conclude by discussing future directions.

Citations

Feb 20, 2020·Current Opinion in Psychiatry·Kevin J LiLynn E DeLisi
Jun 10, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Samuel D ClarkAnissa Abi-Dargham
Jun 4, 2020·Pharmaceuticals·Karol BiernackiSebastian Demkowicz
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga NosovaGeorgy Bakalkin
Jun 26, 2021·Journal of Psychiatric Research·Zeinab Shirvani-FarsaniIman Sadeghi
Jun 17, 2020·Current Drug Targets·Hemen S Ved, Gaurav M Doshi
Jul 7, 2021·Addiction·Katherine Herlinger, Anne Lingford-Hughes
Sep 20, 2021·The International Journal of Neuropsychopharmacology·Genís OnaJordi Riba
Dec 8, 2021·Human Brain Mapping·Ehsan Shokri-KojoriNora D Volkow

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