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https://www.readbyqxmd.com/read/28511993/the-expression-of-opioid-genes-in-non-classical-reward-areas-depends-on-early-life-conditions-and-ethanol-intake
#1
Linnea Granholm, Aniruddah Todkar, Sofia Bergman, Kent Nilsson, Erika Comasco, Ingrid Nylander
The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e...
May 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28509375/chronic-nicotine-induced-changes-in-gene-expression-of-delta-and-kappa-opioid-receptors-and-their-endogenous-ligands-in-the-mesocorticolimbic-system-of-the-rat
#2
Muzeyyen Ugur, Egemen Kaya, Oguz Gozen, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. The present study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4 or 0.6 mg/kg/day for six days. Rats were decapitated one hour after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system...
May 16, 2017: Synapse
https://www.readbyqxmd.com/read/28491463/-pro-dopamine-regulation-kb220z%C3%A2-as-a-long-term-therapeutic-modality-to-overcome-reduced-resting-state-dopamine-tone-in-opiate-opioid-epidemic-in-america
#3
K Blum, F Marcelo, K Dushaj, L Fried, R D Badgaiyan
Since it is known that relapse, morality, and hospitalizations have been tied to the presence of the Dopamine D2 Receptor A1 allele, as one example, and carriers of this gene variant have a proclivity to favor amino-acid therapy, it seems intuitive that the incorporation of modalities to provide a balance and or restoration of hypodopaminergia should be considered as a front-line tactic to overcome the current American opiate/opioid epidemic, saving millions from death and unwanted locked-in-addiction. If we continue down the prim road path of fighting addiction to narcotics with narcotics, we are doomed to fail...
September 2016: Journal of Systems and Integrative Neuroscience
https://www.readbyqxmd.com/read/28472364/association-between-polymorphisms-in-the-purinergic-p2y12-receptor-gene-and-severity-of-both-cancer-pain-and-postoperative-pain
#4
Masahiko Sumitani, Daisuke Nishizawa, Makoto Nagashima, Kazutaka Ikeda, Hiroaki Abe, Ryoji Kato, Hiroshi Ueda, Yoshitsugu Yamada
Background.:  Despite the widespread use of opioids for the treatment of cancer pain, results from several surveys consistently show that pain is still prevalent in some patients with malignant diseases. The purinergic P2Y12 receptor is a primary site leading to microglial activation and hyperalgesic pain behaviors and is considered a key regulator in the prevention of the aggravation of clinical pain conditions. Genetic variability in the P2RY12 gene may contribute to individual differences in pain and opioid sensitivity...
May 4, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28470102/oct1-genetic-variants-are-associated-with-postoperative-morphine-related-adverse-effects-in-children
#5
Rajiv Balyan, Xue Zhang, Vidya Chidambaran, Lisa J Martin, Tomoyuki Mizuno, Tsuyoshi Fukuda, Alexander A Vinks, Senthilkumar Sadhasivam
AIM: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28462386/association-of-variants-of-arginine-vasopressin-and-arginine%C3%A2-vasopressin-receptor-1a-with-severe-acetaminophen%C3%A2-liver-injury
#6
Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M Lee
BACKGROUND & AIMS: Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. METHODS: We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28461466/oxytocin-under-opioid-antagonism-leads-to-supralinear-enhancement-of-social-attention
#7
Olga Dal Monte, Matthew Piva, Kevin M Anderson, Marios Tringides, Avram J Holmes, Steve W C Chang
To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28457972/the-rewarding-effects-of-ethanol-are-modulated-by-binge-eating-of-a-high-fat-diet-during-adolescence
#8
M Carmen Blanco-Gandía, Juan Carlos Ledesma, Auxiliadora Aracil-Fernández, Francisco Navarrete, Sandra Montagud-Romero, Maria A Aguilar, Jorge Manzanares, José Miñarro, Marta Rodríguez-Arias
Binge-eating is considered a specific form of overeating characterized by intermittent and high caloric food intake in a short period of time. Epidemiologic studies support a positive relation between the ingestion of fat and ethanol (EtOH), specifically among adolescent subjects. The aim of this work was to clarify the role of the compulsive, limited and intermittent intake of a high-fat food during adolescence on the rewarding effects of EtOH. After binge-eating for 2 h, three days a week from postnatal day (PND) 29, the reinforcing effects of EtOH were tested with EtOH self-administration (SA), conditioned place preference (CPP) and ethanol locomotor sensitization procedures in young adult mice...
April 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28456841/changes-in-gene-expression-and-sensitivity-of-cocaine-reward-produced-by-a-continuous-fat-diet
#9
M Carmen Blanco-Gandía, Auxiliadora Aracil-Fernández, Sandra Montagud-Romero, Maria A Aguilar, Jorge Manzanares, José Miñarro, Marta Rodríguez-Arias
RATIONALE: Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. OBJECTIVES: The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed. METHODS: Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69...
April 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28456745/oprm1-methylation-contributes-to-opioid-tolerance-in-cancer-patients
#10
Chi T Viet, Dongmin Dang, Bradley E Aouizerat, Christine Miaskowski, Yi Ye, Dan T Viet, Kentaro Ono, Brian L Schmidt
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that both chronic cancer pain and high dose opioid use lead to mu-opioid receptor down-regulation. In this study we explore down-regulation of OPRM1, the mu-opioid receptor gene, as a mechanism f,or opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients...
April 26, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28441707/fentanyl-inhibits-tumorigenesis-from-human-breast-stem-cells-by-inducing-apoptosis
#11
Nadir Kocak, Filiz Ozen, Ibrahim Halil Yildirim, Yagmur Duran
Fentanyl is an opioid analgesic that it is widely used in cancer patients. Since there have been reports of effects of analgesic medications on the recurrence and development of resistance to treatment, influences of of fentanyl on MCF-7 and HEK293 cells were evaluated. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Gene expression analysis was performed by quantitative real-time PCR assay for the Oct4, Sox2 and Nanog genes as stem cell markers and Bax, Bcl2, and p53 genes as apoptosis markers...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28439935/neonatal-immune-challenge-followed-by-adult-immune-challenge-induces-epigenetic-susceptibility-to-aggravated-visceral-hypersensitivity
#12
J E Aguirre, J H Winston, S K Sarna
BACKGROUND: Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). The inflammatory mediators released by colon inflammation are known to sensitize the afferent neurons, which is one of the contributors to abdominal pain. However, not all IBD patients have abdominal pain, and some patients report abdominal pain during remission, suggesting contributions of other pathological factors to abdominal pain in IBD. Epidemiological studies found early-life gastrointestinal infections a risk factor for IBD symptoms and adult-life gastrointestinal infections may trigger the onset of IBD...
April 25, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28436446/opioid-self-administration-is-attenuated-by-early-life-experience-and-gene-therapy-for-anti-inflammatory-il-10-in-the-nucleus-accumbens-of-male-rats
#13
Michael J Lacagnina, Ashley M Kopec, Stewart S Cox, Richa Hanamsagar, Corinne Wells, Susan Slade, Peter M Grace, Linda R Watkins, Edward D Levin, Staci D Bilbo
Early-life conditions can contribute to the propensity for developing neuropsychiatric disease, including substance abuse disorders. However, the long-lasting mechanisms that shape risk or resilience for drug addiction remain unclear. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation, and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10)...
April 24, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28415063/neuron-restrictive-silencer-factor-mediated-downregulation-of-%C3%AE-opioid-receptor-contributes-to-the-reduced-morphine-analgesia-in-bone-cancer-pain
#14
Chao Zhu, Jun Tang, Tan Ding, Lei Chen, Wei Wang, Xiao-Peng Mei, Xiao-Tao He, Wen Wang, Li-Dong Zhang, Yu-Lin Dong, Zhuo-Jing Luo
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively...
May 2017: Pain
https://www.readbyqxmd.com/read/28407740/mu-opioid-receptor-and-delta-opioid-receptor-differentially-regulate-microglial-inflammatory-response-to-control-proopiomelanocortin-neuronal-apoptosis-in-the-hypothalamus-effects-of-neonatal-alcohol
#15
Pallavi Shrivastava, Miguel A Cabrera, Lucy G Chastain, Nadka I Boyadjieva, Shaima Jabbar, Tina Franklin, Dipak K Sarkar
BACKGROUND: Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus. METHODS: Neonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6...
April 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28404521/diabetic-complications-in-the-cornea
#16
Alexander V Ljubimov
Diabetic corneal alterations, such as delayed epithelial wound healing, edema, recurrent erosions, neuropathy/loss of sensitivity, and tear film changes are frequent but underdiagnosed complications of both type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. The disease affects corneal epithelium, corneal nerves, tear film, and to a lesser extent, endothelium, and also conjunctiva. These abnormalities may appear or become exacerbated following trauma, as well as various surgeries including retinal, cataract or refractive...
April 9, 2017: Vision Research
https://www.readbyqxmd.com/read/28388599/abcb1-genotype-is-associated-with-fentanyl-requirements-in-critically-ill-children
#17
Christopher M Horvat, Alicia K Au, Yvette L Conley, Patrick M Kochanek, Lingjue Li, Samuel L Poloyac, Philip E Empey, Robert S B Clark
BACKGROUND: The gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children. METHODS: A diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study...
April 7, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28380057/specific-behavioral-and-cellular-adaptations-induced-by-chronic-morphine-are-reduced-by-dietary-omega-3-polyunsaturated-fatty-acids
#18
Joshua Hakimian, Ani Minasyan, Lily Zhe-Ying, Mariana Loureiro, Austin Beltrand, Camille Johnston, Alexander Vorperian, Nicole Romaneschi, Waleed Atallah, Fernando Gomez-Pinilla, Wendy Walwyn
Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28379874/effects-of-single-nucleotide-polymorphisms-on-surgical-and-post-surgical-opioid-requirements-a-systematic-review-and-meta-analysis
#19
Siu-Wai Choi, David M H Lam, Stanley S C Wong, Haydn H C Shiu, Amy X M Wang, Chi-Wai Cheung
OBJECTIVES: There is great heterogeneity in the way individuals respond to medications. Inherited differences, such as Single Nucleotide Polymorphisms (SNP), can influence the efficacy and toxicity of drugs. This meta-analysis aims to collate data from studies investigating the effect of SNPs on post-operative and/or intra-operative opioid requirements. METHODS: This meta-analysis was conducted following PRISMA guidelines. Eligibility criteria for studies in this meta-analysis were reporting amount of post-operative and/or intra-operative opioid used as the primary outcome and genotyping patients for SNPs in one of the following genes; OPRM1, CYP2D6, CYP3A4, CYP3A5, COMT, UGT2B7 or ABCB1...
April 4, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28376280/independent-and-interactive-effects-of-oprm1-and-dat1-polymorphisms-on-alcohol-consumption-and-subjective-responses-in-social-drinkers
#20
Elise M Weerts, Gary S Wand, Brion Maher, Xiaoqiang Xu, Mary Ann Stephens, Xiaoju Yang, Mary E McCaul
BACKGROUND: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. METHODS: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol concentrations (0...
April 4, 2017: Alcoholism, Clinical and Experimental Research
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