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gene addiction

Mikyung Kim, Raly James Custodio, Chrislean Jun Botanas, June Bryan de la Peña, Leandro Val Sayson, Arvie Abiero, Zae Young Ryoo, Jae Hoon Cheong, Hee Jin Kim
Drug addiction is a chronic and relapsing brain disorder, influenced by complex interactions between endogenous and exogenous factors. Per2, a circadian gene, plays a role in drug addiction. Previous studies using Per2-knockout mice have shown a role for Per2 in cocaine, morphine and alcohol addiction. In the present study, we investigated the role of Per2 in methamphetamine (METH) addiction using Per2-overexpression and knockout mice. We observed locomotor sensitization responses to METH administration, and rewarding effects using a conditioned place preference test...
August 9, 2018: Addiction Biology
Cinzia Cameli, Elena Bacchelli, Maria De Paola, Giuliano Giucastro, Stefano Cifiello, Ginetta Collo, Maria Michela Cainazzo, Luigi Alberto Pini, Elena Maestrini, Michele Zoli
The role of nicotinic acetylcholine receptors (nAChR) in nicotine dependence (ND) is well established; CHRNA7, encoding the α7 subunit, has a still uncertain role in ND, although it is implicated in a wide range of neuropsychiatric conditions. CHRFAM7A, a hybrid gene containing a partial duplication of CHRNA7, is possibly involved in modulating α7 nAChR function. The aim of this study was to investigate the role of CHRNA7 and CHRFAM7A genetic variants in ND and to test the hypothesis that α7 nAChR variation may modulate the efficacy of varenicline treatment in smoking cessation...
August 8, 2018: European Journal of Human Genetics: EJHG
Magdalena Zygmunt, Marcin Piechota, Jan Rodriguez Parkitna, Michal Korostynski
Analysis of drug-induced gene expression in the brain has long held the promise of revealing the molecular mechanisms of drug actions as well as predicting their long-term clinical efficacy. However, despite some successes, this promise has yet to be fulfilled. Here, we present an overview of the current state of understanding of drug-induced gene expression in the brain and consider the obstacles to achieving a robust prediction of the properties of psychoactive compounds based on gene expression profiles...
August 7, 2018: Genes, Brain, and Behavior
Saeedeh Shojaeepour, Mehdi Fazeli, Zohreh Oghabian, Leyla Pourgholi, Ali Mandegary
Use of lead-adulterated opium has become one of the major sources of lead poisoning in Iran. This study was designed to assess clinical effects and oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The oxidative stress status in 192 opium users with lead poisoning symptoms measured and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and -T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD) rs1800435 polymorphisms were determined using PCR and PCR-RFLP...
August 3, 2018: Food and Chemical Toxicology
Andrew L Eagle, Elizabeth S Williams, Joseph A Beatty, Charles L Cox, Alfred J Robison
Both the function of hippocampal neurons and hippocampus-dependent behaviors are dependent on changes in gene expression, but the specific mechanisms that regulate gene expression in hippocampus are not yet fully understood. The stable, activity-dependent transcription factor ΔFosB plays a role in various forms of hippocampal-dependent learning and in the structural plasticity of synapses onto CA1 neurons. The authors examined the consequences of viral-mediated overexpression or inhibition of ΔFosB on the function of adult mouse hippocampal CA1 neurons using ex vivo slice whole-cell physiology...
July 2018: ENeuro
Antony D Abraham, Selena S Schattauer, Kathryn L Reichard, Joshua H Cohen, Harrison M Fontaine, Allisa J Song, Salina D Johnson, Benjamin B Land, Charles Chavkin
Activation of kappa opioid receptors (KOR) produces analgesia and aversion via distinct intracellular signaling pathways, but whether G protein-biased KOR agonists can be designed to have clinical utility will depend on a better understanding of the signaling mechanisms involved. We found that KOR activation produced conditioned place aversion and potentiated conditioned place preference for cocaine in male and female C57BL/6N mice. Consistent with this, males and females both showed arrestin-mediated increases in phospho-p38 MAPK following KOR activation...
August 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Manuela Spagnuolo, Giulia Regazzo, Marco De Dominici, Andrea Sacconi, Andrea Pelosi, Etleva Korita, Francesco Marchesi, Francesco Pisani, Alessandra Magenta, Valentina Lulli, Iole Cordone, Andrea Mengarelli, Sabrina Strano, Giovanni Blandino, Maria G Rizzo, Bruno Calabretta
MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL1-expressing cells. We investigated whether MYB silencing modulates microRNAs expression in Philadelphia-positive leukemia cells and if MYB-regulated microRNAs are important for the MYB addiction of these cells. 35 microRNAs were modulated by MYB silencing in chronic lymphoid and erythro-myeloid blast crisis BV173 and K562 leukemia cells; 15 of these were concordantly modulated in both lines...
August 3, 2018: Haematologica
Cecilia Scorza, Claudia Piccini, Marcela Martínez Busi, Juan Andrés Abin Carriquiry, Pablo Zunino
A role of the gut microbiota in influencing brain function and emotional disorders has been suggested. However, only a few studies have investigated the gut microbiota in the context of drug addiction.Cocaine can be smoked (i.e., crack or coca paste) and its consumption is associated with a very high abuse liability and toxicity. We have recently reported that cocaine base seized samples contained caffeine and phenacetin as main active adulterants, which may potentiate its motivational, reinforcing, and toxic effects...
July 31, 2018: Neurotoxicity Research
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice...
July 30, 2018: Molecular Neurobiology
Sang-Hoon Song, Won-Jun Jang, Jihye Hwang, Byoungduck Park, Jung-Hee Jang, Young-Ho Seo, Chae Ha Yang, Sooyeun Lee, Chul-Ho Jeong
Methamphetamine (MA) is a highly addictive psychostimulant that disturbs the central nervous system; therefore, diagnosis of MA addiction is important in clinical and forensic toxicology. In this study, a MA self-administration rat model was used to illustrate the gene expression profiling of the rewarding effect caused by MA. RNA-sequencing was performed to examine changes in gene expression in rat whisker follicles collected before self-administration, after MA self-administration, and after withdrawal sessions...
July 30, 2018: Scientific Reports
Yong Zhang, Yupu Liang, Matthew Randesi, Vadim Yuferov, Connie Zhao, Mary Jeanne Kreek
Prescription opioid abuse, for example of oxycodone, is a pressing public health issue. This study focuses on how chronic oxycodone self-administration (SA) affects the reward pathways in the mouse brain. In this study, we tested the hypothesis that the expression of reward-related genes in the ventral and dorsal striatum, areas involved in different aspects of opioid addiction models, was altered within 1 hour after chronic oxycodone SA, using transcriptome-wide sequencing (RNA-seq). Based on results from earlier human genetic and rodent studies, we focused on a set of genes that may be associated with the development of addictive diseases and the rewarding effect of drugs of abuse, primarily in the opioid, stress response and classical neurotransmitter systems...
July 27, 2018: Neuroscience
Ruey-Yun Wang, Hsiu-Ju Chen, Chieh-Liang Huang, Jiun-Yi Wang, Tsui-Er Lee, Hsiang-Yen Lee, Chin-Chuan Hung
Opioid addiction is a major public health issue worldwide. Methadone maintenance treatment (MMT) is used to detoxify users of illicit opiates, but drug relapse is common and associated with poor quality of life (QoL). This study investigated the associations between the GRIN3A, GRM6, and TPH2 genetic variants and QoL in the MMT population. A total of 319 participants were included in the study, and genotyping of GRIN3A, GRM6, and TPH2 genes was performed using the Sequenom iPLEX. Associations between genotypes and the domains of QoL were examined through posthoc analysis with LSMEANS syntax using SAS 9...
2018: PloS One
Betina González, Oscar V Torres, Subramaniam Jayanthi, Natalia Gomez, Máximo H Sosa, Alejandra Bernardi, Francisco J Urbano, Edgar García-Rill, Jean-Lud Cadet, Verónica Bisagno
METH use causes neuroadaptations that negatively impact the prefrontal cortex (PFC) leading to addiction and associated cognitive decline in animals and humans. In contrast, modafinil enhances cognition by increasing PFC function. Accumulated evidence indicates that psychostimulant drugs, including modafinil and METH, regulate gene expression via epigenetic modifications. In this study, we measured the effects of single-dose injections of modafinil and METH on the protein levels of acetylated histone H3 (H3ac) and H4ac, deacetylases HDAC1 and HDAC2, and of the NMDA subunit GluN1 in the medial PFC (mPFC) of mice euthanized 1 h after drug administration...
July 26, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Ruonan Wang, Min Li, Meng Zhao, Dahua Yu, Yu Hu, Corinde E Wiers, Gene-Jack Wang, Nora D Volkow, Kai Yuan
Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and from the substantia nigra (SN) to the dorsal striatum are involved in addiction. However, relatively little is known about the implication of these circuits in Internet gaming disorder (IGD). This study examined the alteration of resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI) -based structural connectivity of VTA/SN circuits in 61 young male participants (33 IGD and 28 healthy controls)...
July 27, 2018: Brain Imaging and Behavior
Gerald A Deehan, Sheketha R Hauser, Bruk Getachew, R Aaron Waeiss, Eric A Engleman, Christopher P Knight, William J McBride, William A Truitt, Richard L Bell, Zachary A Rodd
RATIONALE: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. OBJECTIVES: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption...
July 24, 2018: Psychopharmacology
Laurie Herviou, Giacomo Cavalli, Jerome Moreaux
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that functions as the catalytic subunit of the polycomb repressive complex 2 (PRC2). PRC2 represses gene transcription through tri-methylation of lysine 27 of histone 3 (H3K27me3) by its catalytic subunit EZH2. EZH2 is also involved in normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. The oncogenic addiction of tumor cells to EZH2 represents a therapeutic target in several hematological malignancies and solid cancers...
July 2, 2018: Bulletin du Cancer
Ramon L Ramirez, Vinicio De Jesus Perez, Roham T Zamanian
PURPOSE OF REVIEW: Methamphetamine is a highly addictive drug originally developed for the treatment of neuropsychiatric disorders. At present, the epidemic rise of illicit methamphetamine use has increased the number of patients living with medical complications. Our group has recently identified a definite association between methamphetamine use and pulmonary arterial hypertension (PAH), a life-threatening disease characterized by occlusive vasculopathy and progressive right heart failure...
September 2018: Current Opinion in Pulmonary Medicine
Madiha Ahmed, Ihsan Ul Haq, Muhammad Faisal, Durdana Waseem, Malik Mumtaz Taqi
Single nucleotide polymorphism in OPRM1 gene is associated with hedonic and reinforcing consequences of opioids. Risk and protective alleles may vary in different populations. One hundred healthy controls and 100 opioids (predominantly heroin) addicts from Pakistani origin were genotyped for A118G (N40D) polymorphism in OPRM1. Structural and functional impact of the polymorphism on encoded protein was predicted by in silico analysis. Results show significant association between homozygous GG genotype and opioid addiction in Pakistani population (p value = 0...
July 22, 2018: Journal of Molecular Neuroscience: MN
Scott C Farrow, Mohamed Kamileen, Jessica Meades, Belinda Ameyaw, Youli Xiao, Sarah O'Connor
Monoterpenoid indole alkaloids are a large (ca. 3000 members) and structurally diverse class of metabolites restricted to a limited number of plant families in the order Gentianales. Tabernanthe iboga or iboga (Apocynaceae) is native to western equatorial Africa and has been used in traditional medicine for centuries. Howard Lotsof is credited with bringing iboga to the attention of Western medicine through his accidental discovery that iboga can alleviate opioid withdrawal symptoms. Since this observation, iboga has been investigated for its use in the general management of addiction...
July 20, 2018: Journal of Biological Chemistry
Changjiu Zhao, Stephen C Gammie
Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behaviour and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in the nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to nonparental adult mice to determine whether decreases in Nr1d1 expression in the NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social behaviours and mood-related behaviours...
July 20, 2018: European Journal of Neuroscience
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