scholarly journals In Major Depression, Increased Serum Dynorphin and Kappa Opioid Receptor Levels are Positively Associated with Mu Opioid Receptor Levels and Immune Activation and Are Attenuated by Nicotine Dependence

2019 ◽  
Author(s):  
Hussein Al-Hakeim ◽  
Suhaer Al-Fadhel ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Major Depression ◽  
Nicotine Dependence ◽  
Opioid Receptor ◽  
Immune Activation ◽  
Kappa Opioid Receptor ◽  
Receiver Operating Curve ◽  
Kappa Opioid ◽  
Mu Opioid ◽  
Beta Endorphin ◽  
Opioid Systems

Background: There is now evidence that immune and opioid systems show functional reciprocal relationships and that both systems may participate in the pathophysiology of major depression (MDD). Objective: The present study was carried out to delineate differences between MDD patients and healthy controls in dynorphin and kappa opioid receptor (KORs) in association with levels of β-endorphins and mu opioid receptors (MORs), interleukin-6 (IL-6) and IL-10. Method: The present study recruited 60 drug-free male participants with MDD aged 24-70 year and 30 age-matched healthy males as control group and measured serum levels of dynorphin, KOR, β-endorphin, MOR, IL-6 and IL-10. Results: Serum dynorphin, KOR, β-endorphin and MOR are significantly increased in MDD as compared with controls. The increases in the dynorphin/KOR system and β-endorhin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls, whereby both opioid peptides and cytokines show a bootstrapped (n=2000) area under the receiver operating curve of 0.972. KOR and the dynorphin/KOR system are both significantly decreased in depressed subjects with comorbid nicotine dependence. Conclusion: Our findings suggest that in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorhin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by a) exerting immune regulatory activities attenuating the primary immune response; and b) modulating reward responses and mood as well as emotional and behavioral responses to stress.

In major depression, increased kappa and mu opioid receptor levels are associated with immune activation

2020 ◽  
Vol 32 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Suhaer Zeki Al-Fadhel ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Opioid Receptor ◽  
Immune Activation ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Receiver Operating Curve ◽  
Primary Immune Response ◽  
Mu Opioid ◽  
Simultaneous Activation ◽  
Drug Free ◽  
Inflammatory System

AbstractObjective:This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system.Methods:The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.Results:Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.Conclusion:Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.

scholarly journals Kappa opioid receptor binding in major depression: A pilot study

Synapse ◽  
2018 ◽  
Vol 72 (9) ◽  
pp. e22042 ◽  
Author(s):  
Jeffrey M. Miller ◽  
Francesca Zanderigo ◽  
Priya D. Purushothaman ◽  
Christine DeLorenzo ◽  
Harry Rubin-Falcone ◽  
...  
Keyword(s):  
Pilot Study ◽  
Major Depression ◽  
Opioid Receptor ◽  
Receptor Binding ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Opioid Receptor Binding

scholarly journals EXPRESS: Functional bias of morphine and oliceridine under conditions of minor injury

2021 ◽  
pp. 174480692098844
Author(s):  
Chinwe Nwaneshiudu ◽  
Xiao-You Shi ◽  
Peyman Sahbaie ◽  
J. David Clark
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Opioid Receptor ◽  
Medial Prefrontal Cortex ◽  
Receptor Activation ◽  
Kappa Opioid Receptor ◽  
Opioid Antagonist ◽  
Opioid Agonist ◽  
Kappa Opioid ◽  
Mu Opioid

Recent reports suggest pain from surgical injury may influence the risks associated with exposure to opioids. In mice, hind-paw incision attenuates morphine-primed reinstatement due to kappa opioid receptor activation by dynorphin. In this focused group of studies, we examined the hypotheses that kappa-opioid receptor activation in the nucleus accumbens mediates attenuated drug- primed reinstatement after incisional surgery, and the G-protein biased mu-opioid agonist, oliceridine, leads to less priming of the dynorphin effect in comparison to morphine. To address these hypotheses, adult C57BL/6 male mice underwent intracranial cannulation for administration of the selective kappa-opioid antagonist norBNI directly into the nucleus accumbens. After recovery, they were conditioned with morphine or oliceridine after hind-paw incisional injury, then underwent extinction followed by opioid-primed reinstatement. Intra-accumbal administration of norBNI was carried out prior to testing. The nucleus accumbens and medial prefrontal cortex were extracted and analyzed for expression of prodynorphin. We observed that animals conditioned with morphine in the setting of incisional injury demonstrated blunted responses to opioid-primed reinstatement, and that the blunted responses were reversed with intra-accumbal norBNI administration. Persistently elevated levels of prodynorphin expression in the medial prefrontal cortex and nucleus accumbens were observed in the incised morphine-treated animals. However, both behavioral and molecular changes were absent in animals with incisional injury conditioned with oliceridine. These findings suggest a role for prodynorphin expression in the nucleus accumbens with exposure to morphine after surgery that may protect individuals from relapse not shared with biased mu- opioid receptor agonists.

scholarly journals Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators

2021 ◽  
Author(s):  
Huiqun Wang ◽  
Danni Cao ◽  
James C Gillespie ◽  
Rolando E Mendez ◽  
Dana E Selley ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Opioid Receptor ◽  
Binding Mode ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Allosteric Site ◽  
Kappa Opioid ◽  
Mu Opioid ◽  
Mixed Action ◽  
Putative Mechanism

The modulation and selectivity mechanisms of seven mixed-action kappa opioid receptor (KOR)/mu opioid receptor (MOR) bitopic modulators were explored. Molecular modeling results indicated that the ‘message’ moiety of seven bitopic modulators shared the same binding mode with the orthosteric site of the KOR and MOR, whereas the ‘address’ moiety bound with different subdomains of the allosteric site of the KOR and MOR. The ‘address’ moiety of seven bitopic modulators bound to different subdomains of the allosteric site of the KOR and MOR may exhibit distinguishable allosteric modulations to the binding affinity and/or efficacy of the ‘message’ moiety. Moreover, the 3-hydroxy group on the phenolic moiety of the seven bitopic modulators induced selectivity to the KOR over the MOR.

scholarly journals 131 A Marionettist Pulling My Strings: A Case of Buprenorphine-induced Chorea

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 282-283
Author(s):  
Dev Patel ◽  
Ishandeep Gandhi ◽  
Faisal Malek ◽  
Camille Olechowski ◽  
Alan R. Hirsch
Keyword(s):  
Basal Ganglia ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Activation ◽  
Mu Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Mu Opioid ◽  
Palmar Erythema ◽  
History Of

Abstract:Introduction:Choreaform movements provoked by opiates is an infrequent adverse event. Buprenorphine induction of chorea has not heretofore been described. Such a case is presented.METHOD:Case Study: A 38-year-old female presented with a decade long history of alcohol, cocaine, benzodiazepine, and heroin abuse. The patient was insufflating 1.5 grams of heroin daily. On presentation, she was actively withdrawing, scoring 17 on the Clinical Opioid Withdrawal Scale. Urine toxicology screening was positive for opiates, cocaine, and cannabinoids. Buprenorphine 4 mg sublingual was initiated. Within one hour, she observed, “My legs were moving uncontrollably as if I was a marionette.” These dance-like movements were isolated to both legs and gradually resolved after discontinuation of buprenorphine: most of the movements manifested in the first 8 hours, and dissipated over the next 2 days. She did have similar movements after treatment with quetiapine during a previous hospitalization, years earlier.RESULTS:Abnormalities in physical examination: General: goiter, bilateral palmar erythema. Neurological examination: Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test: 2 (anosmia). Motor Examination: Drift testing: mild right pronator drift. Reflexes: 3+ bilateral lower extremities. Neuropsychiatric Examination: Clock Drawing Test: 3 (abnormal). Animal Fluency Test: 18 (normal). Go-No-Go Test 6/6 (normal).DISCUSSION:Buprenorphine induced chorea could be a result of partial mu-opioid agonism, or kappa and delta receptor antagonism (Burke, 2018; Cowan, 1977). Mu-opioid receptor activation causes increased dopamine turnover in the nigrostriatum, which is responsible for locomotor sensitization (Campos-Jurado, 2017). With the addition of mu-opioid receptor modulation of dopamine release, kappa-opioid receptor alters various neurotransmitters in the basal ganglia, potentiating hyperkinetic movements. Buprenorphine’s choreiformogenic action may be due to kappa-opioid receptors ability to augment neurotransmission in the striatum (Escobar, 2017; Bonnet, 1998). The combination of simultaneous activity of these three opioid receptors may cause chorea, since they act to modulate dopamine, glutamate, and GABA in the direct and indirect pathways within the basal ganglia (Abin, 1989; Cui, 2013; Allouche, 2014; Trifilieff, 2013). This patient’s history of heroin and cocaine use may have caused supersensitization of dopamine receptors (Memo, 1981), provoking hyperkinesia. Involvement of substance-induced sensitization with concurrent kappa-opioid receptor neurotransmitter augmentation in direct and indirect pathways in the basal ganglia may have primed our patient to the development of chorea after buprenorphine administration. Further investigation for the presence of extrapyramidal movements in those undergoing buprenorphine treatment is warranted.

New C(2)-sulfonyl ester-type Salvinorin A ligands to the kappa-opioid receptor

Planta Medica ◽  
2015 ◽  
Vol 81 (05) ◽  
Author(s):  
PR Polepally ◽  
A Keasling ◽  
K White ◽  
E Vardy ◽  
BL Roth ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Salvinorin A ◽  
Kappa Opioid
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