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https://www.readbyqxmd.com/read/29216597/role-of-dopamine-receptors-in-the-anticancer-activity-of-onc201
#1
Christina Leah B Kline, Marie B Ralff, Amriti R Lulla, Jessica M Wagner, Phillip H Abbosh, David T Dicker, Joshua E Allen, Wafik S El-Deiry
ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type-specific manner...
December 4, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29205397/effects-of-long-term-alcohol-drinking-on-the-dopamine-d2-receptor-gene-expression-and-heteroreceptor-complexes-in-the-striatum-in-rats
#2
Kristin Feltmann, Dasiel Oscar Borroto-Escuela, Joëlle Rüegg, Luca Pinton, Thatiane de Oliveira Sergio, Manuel Narváez, Antonio Jimenez-Beristain, Tomas J Ekström, Kjell Fuxe, Pia Steensland
BACKGROUND: Reduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent. METHODS: A validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naïve control rats...
December 5, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29205277/clinical-and-genetic-factors-are-associated-with-pain-and-hospitalisation-rates-in-sickle-cell-anaemia-in-cameroon
#3
Ambroise Wonkam, Khuthala Mnika, Valentina J Ngo Bitoungui, Bernard Chetcha Chemegni, Emile R Chimusa, Collet Dandara, Andre P Kengne
We aimed to investigate the clinical and genetic predictors of painful vaso-occlusive crises (VOC) in sickle cell disease (SCD) in Cameroon. Socio-demographics, clinical variables/events and haematological indices were acquired. Genotyping was performed for 40 variants in 17 pain-related genes, three fetal haemoglobin (HbF)-promoting loci, two kidney dysfunctions-related genes, and HBA1/HBA2 genes. Statistical models using regression frameworks were performed in R® . A total of 436 hydoxycarbamide- and opioid-naïve patients were studied; median age was 16 years...
December 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29191473/dopamine-receptors-and-bdnf-haplotypes-predict-dyskinesia-in-parkinson-s-disease
#4
Cynthia D J Kusters, Kimberly C Paul, Ilaria Guella, Jeff M Bronstein, Janet S Sinsheimer, Matt J Farrer, Beate R Ritz
OBJECTIVE: Dyskinesia is a known side-effect of the treatment of Parkinson's Disease (PD). We examined the influence of haplotypes in three dopamine receptors (DRD1, DRD2 and DRD3) and the Brain Derived Neurotrophic Factor (BDNF) on dyskinesia. METHODS: Patient data were drawn from a population-based case-control study. We included 418 patients with confirmed diagnoses by movement disorder specialists, using levodopa and a minimum three years disease duration at the time of assessment...
November 24, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29181280/associations-of-igf2-and-drd2-polymorphisms-with-laying-traits-in-muscovy-duck
#5
Qiao Ye, Jiguo Xu, Xinfeng Gao, Hongjia Ouyang, Wei Luo, Qinghua Nie
Insulin-like growth factor 2 (IGF2) and dopamine receptor 2 (DRD2) play important roles in ovarian follicular development. In this study, we analyzed tissue-specific expression of the Muscovy duck IGF2 and DRD2 genes and cloned those genes transcripts. Polymorphisms in these genes were tightly linked with egg production traits and both genes were highly expressed in the ovary. Moreover, we identified five single nucleotide polymorphisms (SNPs) for IGF1 and 28 for DRD2. Mutations A-1864G and C-1704G of IGF2 were positively correlated with increased egg laying at 59 weeks (E59W) (P < 0...
2017: PeerJ
https://www.readbyqxmd.com/read/29169998/interaction-between-drd2-and-lead-exposure-on-the-cortical-thickness-of-the-frontal-lobe-in-youth-with-attention-deficit-hyperactivity-disorder
#6
Johanna Inhyang Kim, Jae-Won Kim, Jong-Min Lee, Hyuk Jin Yun, Chul-Ho Sohn, Min-Sup Shin, Bongseog Kim, Jonghee Chae, Jaewoo Roh, Bung-Nyun Kim
BACKGROUND: The dopamine receptor D2 receptor (DRD2) gene and lead exposure are both thought to contribute to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). ADHD is characterized by delay in brain maturation, most prominent in the prefrontal cortex (PFC). The D2 receptor is also mainly located in the PFC, and animal studies show that lead exposure affects the dopaminergic system of the frontal lobe, indicating an overlap in neural correlates of ADHD, DRD2, and lead exposure...
November 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29167485/sleep-deprivation-diminishes-attentional-control-effectiveness-and-impairs-flexible-adaptation-to-changing-conditions
#7
Paul Whitney, John M Hinson, Brieann C Satterfield, Devon A Grant, Kimberly A Honn, Hans P A Van Dongen
Insufficient sleep is a global public health problem resulting in catastrophic accidents, increased mortality, and hundreds of billions of dollars in lost productivity. Yet the effect of sleep deprivation (SD) on decision making and performance is often underestimated by fatigued individuals and is only beginning to be understood by scientists. The deleterious impact of SD is frequently attributed to lapses in vigilant attention, but this account fails to explain many SD-related problems, such as loss of situational awareness and perseveration...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156812/correlation-of-drd2-mrna-expression-levels-with-deficit-syndrome-severity-in-chronic-schizophrenia-patients-receiving-clozapine-treatment
#8
Liang Liu, Yin Luo, Guofu Zhang, Chunhui Jin, Zhenhe Zhou, Zaohuo Cheng, Guozhen Yuan
Schizophrenia is a complex, severe, chronic psychiatric disorder, and the associated deficit syndrome is widely regarded as an important clinical aspect of schizophrenia. This study analyzed the relationship of deficit syndrome severity with the mRNA levels of members of signaling pathways that associate with the pathophysiology of schizophrenia, including the dopamine D2 receptor (DRD2), protein kinase B (AKT1), and phosphoinositide-3 kinase (PI3KCB), in peripheral blood leukocytes (PBLs) of 20 healthy controls and 19 chronic schizophrenia patients with long-term clozapine treatment...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141007/escitalopram-and-nht-normalized-stress-induced-anhedonia-and-molecular-neuroadaptations-in-a-mouse-model-of-depression
#9
Or Burstein, Motty Franko, Eyal Gale, Assaf Handelsman, Segev Barak, Shai Motsan, Alon Shamir, Roni Toledano, Omri Simhon, Yafit Hirshler, Gang Chen, Ravid Doron
Anhedonia is defined as a diminished ability to obtain pleasure from otherwise positive stimuli. Anxiety and mood disorders have been previously associated with dysregulation of the reward system, with anhedonia as a core element of major depressive disorder (MDD). The aim of the present study was to investigate whether stress-induced anhedonia could be prevented by treatments with escitalopram or novel herbal treatment (NHT) in an animal model of depression. Unpredictable chronic mild stress (UCMS) was administered for 4 weeks on ICR outbred mice...
2017: PloS One
https://www.readbyqxmd.com/read/29135816/dopaminergic-genetic-variants-and-voluntary-externally-paced-exercise-behavior
#10
Denise J van der Mee, Iryna O Fedko, Jouke-Jan Hottenga, Erik A Ehli, Matthijs D van der Zee, Lannie Ligthart, Toos C E M van Beijsterveldt, Gareth E Davies, Meike Bartels, Joseph G Landers, Eco J C de Geus
PURPOSE: Most candidate gene studies on the neurobiology of voluntary exercise behavior have focused on the dopaminergic signaling pathway and its role in the mesolimbic reward system. We hypothesized that dopaminergic candidate genes may influence exercise behavior through additional effects on executive functioning and that these effects are only detected when the types of exercise activity are taken into account. METHODS: Data on voluntary exercise behavior and at least one SNP/VNTR were available for 12,929 participants of the Netherlands Twin Registry...
November 9, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29108778/the-timing-and-duration-of-estradiol-treatment-in-a-rat-model-of-the-perimenopause-influences-on-social-behavior-and-the-neuromolecular-phenotype
#11
Alexandra N Garcia, Christina Depena, Kelsey Bezner, Weiling Yin, Andrea C Gore
This study tested the effects of timing and duration of estradiol (E2) treatment, factors that are clinically relevant to hormone replacement in perimenopausal women, on social behavior and expression of genes in brain regions that regulate these behaviors. Female rats were ovariectomized (OVX) at 1year of age, roughly equivalent to middle-age in women, and given E2 or vehicle for different durations (3 or 6months) and timing (immediately or after a 3-month delay) relative to OVX. Social and ultrasonic vocalization (USV) behaviors were assessed at the 3 and 6month timepoints, and the rats' brains were then used for gene expression profiling in hypothalamus (supraoptic nucleus, paraventricular nucleus), bed nucleus of the stria terminalis, medial amygdala, and prefrontal cortex using a 48-gene qPCR platform...
November 8, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/29108308/a-phase-2-study-of-the-first-imipridone-onc201-a-selective-drd2-antagonist-for-oncology-administered-every-three-weeks-in-recurrent-glioblastoma
#12
Isabel Arrillaga-Romany, Andrew S Chi, Joshua E Allen, Wolfgang Oster, Patrick Y Wen, Tracy T Batchelor
ONC201 is an oral, small molecule selective antagonist of the G protein-coupled receptor DRD2 that causes p53-independent apoptosis in tumor cells via integrated stress response activation and Akt/ERK inactivation. We performed a Phase II study that enrolled 17 patients with recurrent, bevacizumab-naïve, IDH1/2 WT glioblastoma who received 625mg ONC201 every three weeks. Median OS was 41.6 weeks with OS6 of 71% and OS9 of 53%. Seven of 17 patients are alive. PFS6 was 11.8% with two patients remaining on study who continue to receive ONC201 for >12 months...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107444/dopamine-d2l-receptor-interacting-proteins-regulate-dopaminergic-signaling
#13
REVIEW
Norifumi Shioda
Dopamine receptor family proteins include seven transmembrane and trimeric GTP-binding protein-coupled receptors (GPCRs). Among them, the dopamine D2 receptor (D2R) is most extensively studied. All clinically used antipsychotic drugs serve as D2R antagonists in the mesolimbic dopamine system, and their ability to block D2R signaling is positively correlated with antipsychotic efficiency. Human genetic studies also show a significant association of DRD2 polymorphisms with disorders including schizophrenia and Parkinson's disease...
October 14, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29102591/hippocampal-gene-expression-patterns-in-oxytocin-male-knockout-mice-are-related-to-impaired-social-interaction
#14
Virginia Meneghini Lazzari, Josi Maria Zimmermann-Peruzatto, Grasiela Agnes, Roberta Oriques Becker, Ana Carolina de Moura, Silvana Almeida, Renata Padilha Guedes, Marcia Giovenardi
Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC)...
November 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29093669/cocaine-and-caffeine-effects-on-the-conditioned-place-preference-test-concomitant-changes-on-early-genes-within-the-mouse-prefrontal-cortex-and-nucleus-accumbens
#15
Javier A Muñiz, José P Prieto, Betina González, Máximo H Sosa, Jean L Cadet, Cecilia Scorza, Francisco J Urbano, Verónica Bisagno
Caffeine is the world's most popular psychostimulant and is frequently used as an active adulterant in many illicit drugs including cocaine. Previous studies have shown that caffeine can potentiate the stimulant effects of cocaine and cocaine-induced drug seeking behavior. However, little is known about the effects of this drug combination on reward-related learning, a key process in the maintenance of addiction and vulnerability to relapse. The goal of the present study was thus to determine caffeine and cocaine combined effects on the Conditioned Place Preference (CPP) test and to determine potential differential mRNA expression in the Nucleus Accumbens (NAc) and medial prefrontal cortex (mPFC) of immediate-early genes (IEGs) as well as dopamine and adenosine receptor subunits...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29071300/dopamine-d2-receptors-in-the-paraventricular-thalamus-attenuate-cocaine-locomotor-sensitization
#16
Abigail M Clark, Felix Leroy, Kelly M Martyniuk, Wendy Feng, Erika McManus, Matthew R Bailey, Jonathan A Javitch, Peter D Balsam, Christoph Kellendonk
Alterations in thalamic dopamine (DA) or DA D2 receptors (D2Rs) have been measured in drug addiction and schizophrenia, but the relevance of thalamic D2Rs for behavior is largely unknown. Using in situ hybridization and mice expressing green fluorescent protein (GFP) under the Drd2 promoter, we found that D2R expression within the thalamus is enriched in the paraventricular nucleus (PVT) as well as in more ventral midline thalamic nuclei. Within the PVT, D2Rs are inhibitory as their activation inhibits neuronal action potentials in brain slices...
September 2017: ENeuro
https://www.readbyqxmd.com/read/29057276/genetic-correlates-of-spirituality-religion-and-depression-a-study-in-offspring-and-grandchildren-at-high-and-low-familial-risk-for-depression
#17
Micheline R Anderson, Lisa Miller, Priya Wickramaratne, Connie Svob, Zagaa Odgerel, Ruixin Zhao, Myrna M Weissman
RATIONALE: Possible genetic correlates of spirituality and depression have been identified in community samples. We investigate some of the previously identified candidates in a sample of families at both high and low-risk for depression. METHOD: Offspring and grandchildren of individuals at high and low-risk for depression, participating in a multi-wave thirty-year longitudinal study, were assessed for seven SNPS drawn from four single gene candidates associated with systems implicated in both depression and spirituality: Serotonin (5-HT1B and 5-HT2A), Dopamine (DRD2), Oxytocin (OT) and Monoamine Vesicular Transporter (VMAT1)...
March 2017: Spirituality in Clinical Practice
https://www.readbyqxmd.com/read/29054034/an-exploration-of-common-dopaminergic-variants-and-behavior-problems-in-siblings-at-high-risk-for-autism-spectrum-disorder
#18
Devon N Gangi, Lauren V Usher, Daniel S Messinger
Younger siblings of children with ASD often exhibit elevated internalizing and externalizing problems. We investigated common dopaminergic variants (DRD4 and DRD2) in relation to behavior problems at 36 months. Genotypes linked to less efficient dopaminergic functioning were associated with higher internalizing problems in high-risk siblings.
October 17, 2017: Infant Behavior & Development
https://www.readbyqxmd.com/read/29042896/genome-wide-supported-risk-variants-in-mir137-cacna1c-csmd1-drd2-and-grm3-contribute-to-schizophrenia-susceptibility-in-pakistani-population
#19
Ambrin Fatima, Muhammad Farooq, Uzma Abdullah, Muhammad Tariq, Tanveer Mustafa, Muhammad Iqbal, Niels Tommerup, Shahid Mahmood Baig
OBJECTIVE: Schizophrenia is a chronic neuropsychiatric disease afflicting around 1.1% of the population worldwide. Recently, MIR137, CACNA1C, CSMD1, DRD2, and GRM3 have been reported as the most robustly emerging candidates involved in the etiology of schizophrenia. In this case control study, we performed an association analysis of rs1625579 (MIR137), rs1006737, rs4765905 (CACNA1C), rs10503253 (CSMD1), rs1076560 (DRD2), rs12704290, rs6465084, and rs148754219 (GRM3) in Pakistani population...
September 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/29039297/the-impact-of-periconceptional-alcohol-exposure-on-fat-preference-and-gene-expression-in-the-mesolimbic-reward-pathway-in-adult-rat-offspring
#20
E S Dorey, C L Cullen, D Lucia, K M Mah, M-L Roy Manchadi, B S Muhlhausler, K M Moritz
Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring...
October 17, 2017: Journal of Developmental Origins of Health and Disease
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