scholarly journals Repeated Ethanol Exposure Alters DNA Methylation Status and Dynorphin/Kappa-Opioid Receptor Expression in Nucleus Accumbens of Alcohol-Preferring AA Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Kerly Niinep ◽  
Kaili Anier ◽  
Tony Eteläinen ◽  
Petteri Piepponen ◽  
Anti Kalda
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Opioid Receptor ◽  
Wistar Rats ◽  
Kappa Opioid Receptor ◽  
Mrna Levels ◽  
Kappa Opioid ◽  
Receptor System ◽  
Ethanol Group ◽  
Aberrant Dna Methylation

Growing evidence suggests that epigenetic mechanisms, such as DNA methylation and demethylation, and histone modifications, are involved in the development of alcohol and drug addiction. However, studies of alcohol use disorder (AUD) that are focused on epigenetic DNA modifications and gene expression changes remain conflicting. Our aim was to study the effect of repeated ethanol consumption on epigenetic regulatory enzymes such as DNA methyltransferase and demethylase enzymes and whether those changes affected dynorphin/kappa-opioid receptor system in the Nucleus Accumbens (NAc). Two groups of male alcohol-preferring Alko Alcohol (AA) rats, rats which are selectively bred for high voluntary alcohol consumption and one group of male Wistar rats were used. The first group of AA rats had access to alcohol (10% ethanol solution) for 90 min on Mondays, Wednesdays and Fridays over a period of 3 weeks to establish a stable baseline of ethanol intake (AA-ethanol). The second group of AA rats (AA-water) and the Wistar rats (Wistar-water) were provided with water. Using qPCR, we found that voluntary alcohol drinking increased Dnmt1, −3a, and −3b mRNA levels and did not affect Tet family transcripts in the AA-ethanol group when compared with AA- and Wistar-water rats. DNMT and TET enzymatic activity measurements showed similar results to qPCR, where DNMT activity was increased in AA-ethanol group compared with AA-water and Wistar-water groups, with no statistically significant difference between groups in TET enzyme activity. In line with previous data, we found an increased percentage of global DNA methylation and hydroxymethylation in the AA-ethanol group compared with control rats. Finally, we investigated changes of selected candidate genes from dynorphin/kappa-opioid receptor system (Pdyn, Kor) and Dnmt3a genes that might be important in AUD-related behaviour. Our gene expression and promoter methylation analysis revealed a significant increase in the mRNA levels of Pdyn, Kor, and Dnmt3a in the AA-ethanol group, however, these changes can only be partially associate with the aberrant DNA methylation in promoter areas of the selected candidate genes. Thus, our findings suggest that the aberrant DNA methylation is rather one of the several mechanisms involved in gene expression regulation in AA rat model.

scholarly journals Does the kappa opioid receptor system contribute to pain aversion?

2014 ◽  
Vol 5 ◽  
Author(s):  
Catherine M. Cahill ◽  
Anna M. W. Taylor ◽  
Christopher Cook ◽  
Edmund Ong ◽  
Jose A. Morón ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Receptor System

Considerations on Using Antibodies for Studying the Dynorphins/Kappa Opioid Receptor System

2021 ◽  
pp. 23-38
Author(s):  
Chongguang Chen ◽  
Melanie Widmann ◽  
Christoph Schwarzer ◽  
Lee-Yuan Liu-Chen
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Receptor System

Acute intermittent morphine increases preprodynorphin and kappa opioid receptor mRNA levels in the rat brain

1999 ◽  
Vol 66 (1-2) ◽  
pp. 184-187 ◽  
Author(s):  
Xiao-Min Wang ◽  
Yan Zhou ◽  
Rudolph Spangler ◽  
Ann Ho ◽  
Ji-Shen Han ◽  
...  
Keyword(s):  
Rat Brain ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Mrna Levels ◽  
Kappa Opioid ◽  
Receptor Mrna

scholarly journals Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hurramhon Shokirova ◽  
Takenori Inomata ◽  
Tsuyoshi Saitoh ◽  
Jun Zhu ◽  
Kenta Fujio ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Topical Administration ◽  
Corneal Neovascularization ◽  
Kappa Opioid Receptor ◽  
Inflammatory Factors ◽  
Corneal Transplant ◽  
Mrna Levels ◽  
Kappa Opioid ◽  
Opioid Receptor Agonist

AbstractCorneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans.

scholarly journals nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Erin Harshberger ◽  
Emily A. Gilson ◽  
Kelli Gillett ◽  
Jasmine H. Stone ◽  
Laila El Amrani ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Wistar Rats ◽  
Ethanol Solution ◽  
Kappa Opioid Receptor ◽  
Opioid Agonist ◽  
Kappa Opioid ◽  
Seeking Behavior ◽  
Male Wistar Rats ◽  
Kappa Opioid Agonist ◽  
Time Point

Recent work suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI) to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0.1–10 mg/kg, i.p.) or saline and were tested for the reinstatement of ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist naltrexone (0 or 3.0 mg/kg, s.c.) and nor-BNI (0 or 20.0 mg/kg, i.p.) to block U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated responding on the previously ethanol-associated lever. Pretreatment with naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also attenuated KOR agonist-induced reinstatement, but to a lesser extent than naltrexone, when injected 24 hours prior to injections of U50,488, a time point that is consistent with KOR selectivity. While these results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, U50,488-induced reinstatement may not be fully selective for KORs.

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