scholarly journals Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

2021 ◽  
pp. 026988112199199 ◽  
Author(s):  
Miriam Sebold ◽  
Maria Garbusow ◽  
Deniz Cerci ◽  
Ke Chen ◽  
Christian Sommer ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Opioid Receptor ◽  
Mechanistic Model ◽  
Critical Role ◽  
Opioid System ◽  
Operant Behaviour ◽  
Oprm1 Gene ◽  
Potential Biomarker ◽  
A118g Polymorphism

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Alcohol Dependence Conceptualized as a Stress Disorder

2019 ◽  
pp. 198-220
Author(s):  
Leandro F. Vendruscolo ◽  
George F. Koob
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Glucocorticoid Receptors ◽  
Critical Role ◽  
Emotional States ◽  
Brain Circuits ◽  
Negative Emotional State ◽  
Alcohol Alcohol

Alcohol use disorder is a chronically relapsing disorder that involves (1) compulsivity to seek and take alcohol, (2) difficulty in limiting alcohol intake, and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) in the absence of alcohol. Alcohol addiction encompasses a three-stage cycle that becomes more intense as alcohol use progresses: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages engage neuroadaptations in brain circuits that involve the basal ganglia (reward hypofunction), extended amygdala (stress sensitization), and prefrontal cortex (executive function disorder). This chapter discusses key neuroadaptations in the hypothalamic and extrahypothalamic stress systems and the critical role of glucocorticoid receptors. These neuroadaptations contribute to negative emotional states that powerfully drive compulsive alcohol drinking and seeking. These changes in association with a disruption of prefrontal cortex function that lead to cognitive deficits and poor decision making contribute to the chronic relapsing nature of alcohol dependence.

scholarly journals The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Wound Repair ◽  
Critical Role ◽  
The Novel ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Gastric Cancer Progression

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.

scholarly journals Suppression of Alcohol Preference by Naltrexone in the Rhesus Macaque: A Critical Role of Genetic Variation at the μ-Opioid Receptor Gene Locus

2010 ◽  
Vol 67 (1) ◽  
pp. 78-80 ◽  
Author(s):  
Christina S. Barr ◽  
Scott A. Chen ◽  
Melanie L. Schwandt ◽  
Stephen G. Lindell ◽  
Hui Sun ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Rhesus Macaque ◽  
Opioid Receptor ◽  
Gene Locus ◽  
Receptor Gene ◽  
Critical Role ◽  
Alcohol Preference ◽  
Μ Opioid Receptor

scholarly journals Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Renata Cristina Mendes Ferreira ◽  
Ana Flávia Almeida-Santos ◽  
Igor Dimitri Gama Duarte ◽  
Daniele C. Aguiar ◽  
Fabricio A. Moreira ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Antinociceptive Effect ◽  
Opioid System ◽  
Prostaglandin E ◽  
Intraplantar Injection ◽  
Opioid Receptor Antagonist ◽  
Antinociceptive Effects ◽  
The Right

Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect.Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2injection.Results. Aripiprazole (100 μg/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw), a nonselective opioid receptor antagonist. The role ofμ-,δ-, andκ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw), naltrindole (15, 30, and 60 μg/paw), and nor-binaltorphimine (200 μg/paw), respectively. The data indicated that only theδ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw) aripiprazole-induced peripheral antinociception.Conclusion. The results suggest the participation of the opioid system viaδ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

scholarly journals Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 358-365
Author(s):  
Li Shi ◽  
Ying Wang ◽  
Timothy Bonney Oppong ◽  
Xiaoli Fu ◽  
Haiyan Yang ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Gastrointestinal Cancer ◽  
Web Of Science ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Critical Role ◽  
Clinicopathological Parameters ◽  
Gastrointestinal Cancers ◽  
Potential Biomarker

AbstractSirtuin 6 (SIRT6) plays a critical role in the progression and development of gastrointestinal cancers. However, the association between SIRT6 expression and clinicopathological parameters and prognosis in gastrointestinal cancer patients remains inconclusive. Consequently, we conducted this meta-analysis to evaluate the importance of SIRT6 expression in various types of gastrointestinal cancers. PubMed, EMBASE, and Web of Science databases were systematically searched to screen the relevant literature. The reported or estimated hazard ratio (HR) and odds ratio (OR) and their corresponding 95% confidence interval (CI) were pooled to assess the strength of the association. Nine studies involving 867 patients were included in the meta-analysis. Overall analysis showed that high SIRT6 expression was related to better overall survival in gastrointestinal cancers (HR = 0.62, 95% CI = 0.47–0.82). High SIRT6 expression was also related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% CI = 0.28–0.70) among gastrointestinal cancer patients. Our meta-analysis revealed that high SIRT6 expression might be a potential biomarker predicting better prognosis in gastrointestinal cancers, which may offer options for gastrointestinal cancer treatment.

Critical Role of IL-8 Targeting in Gliomas

2018 ◽  
Vol 25 (17) ◽  
pp. 1954-1967 ◽  
Author(s):  
Marinos Kosmopoulos ◽  
Anthos Christofides ◽  
Dimitrios Drekolias ◽  
Phaedon D. Zavras ◽  
Antonios N. Gargalionis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Response To Therapy ◽  
Molecular Pathways ◽  
Cns Disorders ◽  
Potential Biomarker

Background: Glioma is a heterogeneous, highly complicated central nervous system (CNS) tumor with uncertain mechanism of initiation and progression, resulting in an unfavorable outcome. An extended network of cytokines is recognized as a major regulator of glioma pathogenesis, either promoting or inhibiting glioma progression based on their type and specificity. Interleukin-8 (IL-8) has been revealed as a critical regulator of CNS function and development with participation in many CNS disorders including gliomas. Objective: The aim of the present review is to address the role of IL-8 in glioma pathogenesis focusing on the implicated molecular pathways as well as on its potential targeting for glioma therapy. Methods and Results: PubMed-Medline, SCOPUS, and Google Scholar databases were searched for pre-clinical and clinical studies related to IL-8 implication in gliomagenesis and IL-8 targeting strategies for gliomas. Literature data indicate that IL-8 participates in glioma angiogenesis and cell migration and it can serve as a potential biomarker, for early diagnosis, follow-up and response to therapy. Conclusion: Several promising approaches that target directly or indirectly IL-8 effects in gliomas are currently in progress while more-in-depth studies are needed to validate its biomarker role and elucidate the underlying molecular mechanisms.

scholarly journals Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and δ1-opioid receptor agonists is mediated by iNOS

2005 ◽  
Vol 289 (5) ◽  
pp. H2251-H2257 ◽  
Author(s):  
Yiru Guo ◽  
Adam B. Stein ◽  
Wen-Jian Wu ◽  
Xiaoping Zhu ◽  
Wei Tan ◽  
...  
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Coronary Occlusion ◽  
Critical Role ◽  
No Donors ◽  
Receptor Agonists ◽  
Late Preconditioning ◽  
Opioid Receptor Agonist

Although ischemia-induced late preconditioning (PC) is known to be mediated by inducible nitric oxide (NO) synthase (iNOS), the role of this enzyme in pharmacologically induced late PC remains unclear. We tested whether targeted disruption of the iNOS gene abrogates late PC elicited by three structurally different NO donors [diethylenetriamine/NO (DETA/NO), nitroglycerin (NTG), and S-nitroso- N-acetyl-penicillamine (SNAP)], an adenosine A1 receptor agonist [2-chloro- N6-cyclopentyladenosine (CCPA)], and a δ1-opioid receptor agonist (TAN-670). The mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. In iNOS knockout ( iNOS−/−) mice, infarct size was similar to wild-type (WT) controls, indicating that iNOS does not modulate infarct size in the absence of PC. Pretreatment of WT mice with DETA/NO, NTG, SNAP, TAN-670, or CCPA 24 h before coronary occlusion markedly reduced infarct size. In iNOS−/− mice, however, the late PC effect elicited by DETA/NO, NTG, SNAP, TAN-670, and CCPA was completely abrogated. Furthermore, in WT mice pretreated with TAN-670 or CCPA, the selective iNOS inhibitor 1400W also abolished the delayed PC properties of these drugs; 1400W had no effect in WT mice. These data demonstrate that iNOS plays an obligatory role in NO donor-induced, adenosine A1 receptor agonist-induced, and δ1-opioid receptor agonist-induced late PC, underscoring the critical role of this enzyme as a common mediator of cardiac adaptations to stress.

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