Crosstalk Between Kappa Opioid and Dopamine Systems in Compulsive Behaviors

Escobar, A; Casanova, José Patricio; Andrés, Marı́a Estela; Fuentealba, José Antonio

doi:10.3389/fphar.2020.00057

Cited by 25 publications

(26 citation statements)

References 129 publications

(178 reference statements)

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“…Furthermore, in humans, KOR agonists could produce a dissociative-like syndrome, a state occurring during an inescapable traumatic experience ( Lanius et al, 2018 ). These dysphoric effects are thought to be the consequence of a dopamine (DA) depletion in the reward and the fear circuits ( Karkhanis et al, 2017 ; Lanius et al, 2018 ; Escobar et al, 2020 ). KOR have been found to be expressed in DA neurons of the nucleus accumbens (NAc), the ventral tegmental area (VTA), the caudate putamen and the substantia nigra ( Chen et al, 2020 ).…”

Section: The Dynorphin/kappa-opioid Receptor Systemmentioning

confidence: 99%

“…In this review, we thus focus on both preclinical and clinical research related to the modulation of the KOR system, and its endogenous ligand dynorphin (DYN), in relation with stress and addiction. The interest for this topic has been growing recently ( Helal et al, 2017 ; Karkhanis et al, 2017 ; Jacobson et al, 2018 ; Lanius et al, 2018 ; Valentino and Volkow, 2018 ; Beck et al, 2019 ; Margolis and Karkhanis, 2019 ; Tejeda and Bonci, 2019 ; Anderson, 2020 ; Escobar et al, 2020 ; Nagase and Saitoh, 2020 ). We will thus list here some of the most relevant literature on the DYN/KOR system in pain, dysphoria and psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

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Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System

2022

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Substance use disorders (SUD) may emerge from an individual’s attempt to limit negative affective states and symptoms linked to stress. Indeed, SUD is highly comorbid with chronic stress, traumatic stress, or post-traumatic stress disorder (PTSD), and treatments approved for each pathology individually often failed to have a therapeutic efficiency in such comorbid patients. The kappa-opioid receptor (KOR) and its endogenous ligand dynorphin (DYN), seem to play a key role in the occurrence of this comorbidity. The DYN/KOR function is increased either in traumatic stress or during drug use, dependence acquisition and DYN is released during stress. The behavioural effects of stress related to the DYN/KOR system include anxiety, dissociative and depressive symptoms, as well as increased conditioned fear response. Furthermore, the DYN/KOR system is implicated in negative reinforcement after the euphoric effects of a drug of abuse ends. During chronic drug consumption DYN/KOR functions increase and facilitate tolerance and dependence. The drug-seeking behaviour induced by KOR activation can be retrieved either during the development of an addictive behaviour, or during relapse after withdrawal. DYN is known to be one of the most powerful negative modulators of dopamine signalling, notably in brain structures implicated in both reward and fear circuitries. KOR are also acting as inhibitory heteroreceptors on serotonin neurons. Moreover, the DYN/KOR system cross-regulate with corticotropin-releasing factor in the brain. The sexual dimorphism of the DYN/KOR system could be the cause of the gender differences observed in patients with SUD or/and traumatic stress-related pathologies. This review underlies experimental and clinical results emphasizing the DYN/KOR system as common mechanisms shared by SUD or/and traumatic stress-related pathologies, and suggests KOR antagonist as a new pharmacological strategy to treat this comorbidity.

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Section: The Dynorphin/kappa-opioid Receptor Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System

2022

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“…Moreover, KOR is essential for emotional regulation. Studies have shown that the endogenous opioid peptide dynorphin activates KOR in the nucleus accumbens and KOR agonists inhibit dopamine (DA) transmission ( 86 ). By contrast, KOR antagonists increase the release of basal DA and may produce antidepressant-like effects ( 35 ).…”

Section: Expression and Physiological Function Of Kormentioning

confidence: 99%

Opioids in cancer: The κ‑opioid receptor (Review)

et al. 2021

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The κ-opioid receptor (KOR) is one of the primary receptors of opioids and serves a vital role in the regulation of pain, anesthesia, addiction and other pathological and physiological processes. KOR is associated with several types of cancer and may influence cancer progression. It has been proposed that KOR may represent a new tumor molecular marker and provide a novel basis for molecular targeted therapies for cancer. However, the association between KOR and cancer remains to be explored comprehensively. The present review introduces KOR and its association with different types of cancer. Improved understanding of KOR may facilitate development of novel antitumor therapies. Contents1. Introduction 2. Discovery, structure and typing of KOR 3. Expression and physiological function of KOR 4. Expression, function and significance of KOR in various types of cancer 5. Potential roles of KOR in cancer 6. Effects of opioids on tumors 7. Conclusion and future prospects

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“…The trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide derivative U-50,488 is a selective KOR agonist, possessing analgesic, cough suppressant, and diuretic properties. It also suppresses the psychostimulant reward through the inhibition of dopamine signaling in the addiction pathways [ 10 , 11 , 12 ], with obvious influence in decreasing amphetamine-induced psychomotor disturbances [ 13 ], in preventing cocaine [ 14 ] or nicotine-induced motor troubles [ 15 ], and in reducing the charges of morphine [ 16 ] or fentanyl [ 17 ] self-administration in rodents. Other research has evidenced the beneficial effects of U50,488 on L-dopa attenuation of motor dyskinesia in rodents and primates with experimental-induced Parkinsonian manifestations [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice

et al. 2021

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Background and Objectives: The selective kappa opioid receptor agonist U50,488 was reported to have analgesic, cough suppressant, diuretic and other beneficial properties. The aim of our study was to analyze the effects of some original chitosan-coated liposomes entrapping U50,488 in somatic and visceral nociceptive sensitivity in mice. Materials and Methods: The influence on the somatic pain was assessed using a tail flick test by counting the tail reactivity to thermal noxious stimulation. The nociceptive visceral estimation was performed using the writhing test in order to evaluate the behavioral manifestations occurring as a reaction to the chemical noxious peritoneal irritation with 0.6% acetic acid (10 mL/kbw). The animals were treated orally, at the same time, with a single dose of: distilled water 0.1 mL/10 gbw; 50 mg/kbw U50,488; 50 mg/kbw U50,488 entrapped in chitosan-coated liposomes, according to the group they were randomly assigned. Results: The use of chitosan-coated liposomesas carriers for U50,488 induced antinociceptive effects that began to manifest after 2 h, andwere prolonged but with a lower intensity than those caused by the free selective kappa opioid in both tests. Conclusion: In this experimental model, the oral administration of nanovesicles containing the selective kappa opioid agonist U50,488 determined a prolonged analgesic outcome in the tail flick test, as well as in the writhing test.

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Crosstalk Between Kappa Opioid and Dopamine Systems in Compulsive Behaviors

Abstract: dopamine and sensitized D2R. Thus, the time-dependent activation of KOR impacts directly on dopamine levels affecting the tuning of motivated behaviors. This review analyzes the contribution of the kappa opioid system to the dopaminergic correlates of compulsive behaviors.

Cited by 25 publications

References 129 publications

Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System

Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System

Opioids in cancer: The κ‑opioid receptor (Review)

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice

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