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  • 1
    Keywords: brain ; CANCER ; human ; PHENOTYPES ; STRESS ; INSIGHTS ; CONSUMPTION ; GLUTAMATE ; DRINKING ; DEPENDENCE ; WIDE ASSOCIATION ; Alcoholism ; drug addiction ; genome-wide association study (GWAS) ; GLUTAMATERGIC NEUROTRANSMISSION ; imaging genetics ; NALTREXONE ; QTL analysis ; TRANSPORTER GENE
    Abstract: Alcohol drinking is highly prevalent in many cultures and contributes to the global burden of disease. In fact, it was shown that alcohol constitutes 3.2% of all worldwide deaths in the year 2006 and is linked to more than 60 diseases, including cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders, injuries and foetal alcohol syndrome. Alcoholism, which has been proven to have a high genetic load, is one potentially fatal consequence of chronic heavy alcohol consumption, and may be regarded as one of the most prevalent neuropsychiatric diseases afflicting our society today. The aim of the integrated genome research network 'Genetics of Alcohol Addiction'-which is a German inter-/trans-disciplinary life science consortium consisting of molecular biologists, behavioural pharmacologists, system biologists with mathematicians, human geneticists and clinicians-is to better understand the genetics of alcohol addiction by identifying and validating candidate genes and molecular networks involved in the aetiology of this pathology. For comparison, addictive behaviour to other drugs of abuse (e.g. cocaine) is studied as well. Here, we present an overview of our research consortium, the current state of the art on genetic research in the alcohol field, and list finally several of our recently published research highlights. As a result of our scientific efforts, better insights into the molecular and physiological processes underlying addictive behaviour will be obtained, new targets and target networks in the addicted brain will be defined, and subsequently, novel and individualized treatment strategies for our patients will be delivered
    Type of Publication: Journal article published
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Alcohol as well as other substances of abuse are reinforcing substances which manifest their effects through activation of the mesolimbic dopaminergic reward pathways of the brain. In animal genetic models of alcoholism, reduced dopamine levels and D2 dopamine receptor (DRD2) numbers have been found in the brains of alcohol-preferring animals. Dopamine receptor agonists reduce alcohol consumption, whereas antagonists, in general, show the opposite effect. Moreover, quantitative trait loci studies in animals suggest the DRD2 gene and the region proximate to this locus is a chromosomal “hot spot” for alcohol-related behaviors. Human studies provide additional support for connection between alcohol dependence and CNS dopaminergic function. In endocrinological studies, using dopamine receptor agonists, reduced dopaminergic activity has been found in more severe and more genetic types of alcoholics. Brain imaging studies are similarly revealing a diminished dopaminergic tone in alcoholics. Treatment of alcoholics with dopamine receptor agonists shows reduced alcohol consumption and improvements in other outcome measures. Molecular genetic studies in humans have identified an association of the Al allele of the DRD2 gene with alcoholism. Moreover, a diminished central dopaminergic function has been found in DRD2 A1 allele subjects using pharmacological, electrophysiological and neuropsychological studies. Further, treatment of alcoholics with a dopamine receptor agonist showed more salutary effects on alcoholics who carry than those who do not carry the DRD2 A1 allele. The A1 allele has also been associated with substance use disorders other than alcoholism, including and cocaine and nicotine dependence and polysubstance abuse. The emerging evidence suggests that the DRD2 is a reinforcement or reward gene. It could represent one of the most prominent single-gene determinants of susceptibility to severe substance abuse. However, the environment and other genes, when combined, still play the larger role.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this review we consider some of the practical facets of acute and chronic drug regimes. In particular, we illustrate our arguments with specific reference to alcohol and draw attention to methodological constraints that might alter biochemical or physiological processes. These includes the imposition of nutritional abnormalities and surgical procedures. These two areas are highlighted because there is evidence to show that they have marked influences on metabolic parameters, exemplified by tissue protein synthesis. In general, there is no controversy as to methods for acute studies with alcohol, although some reports have failed to investigate whether intravenous, intragastric or intraperitoneal regimes more accurately mimic the clinical situation. With regard to chronic feeding regimes, evidence is provided to support the argument that, currently, the most appropriate feeding protocol ensures that both control and treated groups receive identical amounts of nutrients albeit with differences in the calories apportioned to ethanol, which is substituted by isocaloric glucose or other carbohydrates in controls. However, there are still other methods being employed: these are subject to misinterpretation as the principle of ensuring that control and ethanol-fed rats receive identical amounts of nutrients, is ignored. In this review we also draw attention to the fact that surgical procedures, which are often employed to facilitate the measurement of body parameters (for example, implantation of cannulae), themselves alter tissue metabolism. The importance of this relates to the concept of metabolic superimposition, which implicates interacting responses when two or more stresses (i.e. surgery and drug administration) are superimposed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Combined anorectic-alcohol misuse is a prevalent problem in Brazil. In order to understand better the interactive effects of ethanol (EtOH) and mazindol (MZ), we examined the effects of EtOH (1.2 g/kg) and MZ (5.0 mg/kg) given alone or in combination, on mouse behaviour. The results indicate that EtOH plus MZ induces a significantly greater increase in locomotor activity of mice than either constituent alone. However, no such interactive effect was detected in the place preference and in the plus-maze test of anxiety. MZ given alone was found to increase the locomotor activity and to possess rewarding effects as measured in the place preference conditioning. At the dose selected, EtOH alone showed anxiolytic and rewarding effects. These results provide some evidence of increased behavioural effects in mice due to combinations of EtOH and MZ. These findings suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by such combination.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ethanol is recognized to affect adversely carbohydrate metabolism in skeletal muscle. This paper seeks to establish whether ethanol acutely impairs glycogen repletion during recovery from high intensity short duration exercise in the rat. High intensity exercise caused the massive mobilization of glycogen stores in muscles rich in type IIa and IIb fibres and marked increases in plasma and muscle lactate levels. During the 30-minute recovery period, there was substantial glycogen repletion in these muscles in both the ethanol-treated and control rats. Ethanol, however, was associated with reduced glycogen resynthesis in both the tibialis anterior (by 22%) and red gastrocnemius (by 31%) muscles but not in the white gastrocnemius muscle. This reduction in post-exercise glycogen deposition was accompanied by decreased lactate disposal and elevated plasma glucose levels. These effects of ethanol on glycogen repletion may involve interactions with hepatic gluconeogenesis, glucose uptake and utilization in muscle, muscle glycogen synthesis and lactate glyconeogenesis. The ethanol-mediated impairment in post-exercise glycogen repletion may have important implications for the pathogenesis of chronic alcoholic skeletal myopathy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Books review in this article: Book reviews in this column will primarily be of titles focusing completely, or in part, on biological aspects of addiction. However, significant titles of general relevance to the addictions field will also be included, even if they are not “biological”, as will titles of general methodological and clinical relevance, even if they are not on “addictions”. Similar considerations will apply to other media (software, audio tapes and CDs, videos, etc). However, specific “addictions” software applications seem to be relatively uncommon and, as these items are rarely reviewed elsewhere, we will endeavour to include reviews of some of the older programmes that are still useful, as well as new titles that appear. I would appreciate suggestions of any items suitable for review, but especially software and other media of specific relevance to the addictions. Enzymology and Molecular Biology of Carbonyl Metabolism 5 H. WIENER, R. S. HOLMES & BENDICHT WERMUTH (Eds) Neurotransmitter Release and its Modulation: Biochemical Mechanisms, Physiological Function and Clinical Relevance D. A. POWIS & S. J. BUNN (Eds) Health Update No. 2—Smoking R. WALTERS & H. WENT Atlas of Clinical Gastroenterology, 2nd edn J. J. MISIEWICZ, A. FORBES, A. B. PRICE, P. J. SHORVON, D. R. TRIGER & G. N. J. TYTGAT Addiction Psychiatry: Current Diagnosis and Treatment N. S. MILLER Clinical Handbook of Psychotropic Drugs—5th revised edn KALYNA Z. BEZCHLIBNYK-BUTLER & J. JOEL JEFFRIES Seminars in Psychiatric Genetics PETER MCGUFFIN, MICHAEL J. OWEN, MICHAEL C. O'DONOVAN, ANITA THAPAR & IRVING I. GOTTESMAN Genetic Analysis: Principles, Scope and Objectives J. R. S. FINCHAM PCR C. R. NEWTON (Ed.) Nucleic Acid Hybridization—Essential data P. M. GILMARTIN CRC Handbook of Chemistry and Physics, 76th edn D. R. LIDE (Ed.) The Biochemists' Songbook—2nd edn HAROLD BAUM SOFTWARE: SPSS for Windows v 6.1 EndNote Plus 2 and EndLink 2 for Windows BodyWorks version 4.0 on CD-ROM Current Awareness in Biological Sciences
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The ability to transfect and express foreign genes in cultured cells and Xenopus oocytes has contributed immensely to our knowledge of drug-receptor interactions and signal transduction following receptor activation. These techniques are now being used to study acute and chronic effects of ethanol on neurotransmitter receptors and cellular signaling. This article reviews the use of transfected cells to study ethanol actions on the GABAA receptor.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A retrospective case control study utilizing birth certificate data in a population of children with Fetal Alcohol Syndrome (FAS) or Fetal Alcohol Effect (FAE) and controls in North Dakota was completed. Using the North Dakota FAS registry, 97 cases of FAS and FAE aged birth-18 years of age were identified. The North Dakota Department of Vital Records then searched for the child's birth certificates. For each case child, four controls were selected from the birth records. The controls were of the same race, sex, month and county of birth as the cases. Birth certificates for 68 children were identified, 44 with FAS and 24 with FAE. When compared with the FAE group, the FAS group had lower birth weights and mothers who began prenatal care later in pregnancy. The FAS/FAE group combined had mothers who were older, were more likely to be unmarried, had less weight gain during pregnancy, started prenatal care later in pregnancy and had fewer prenatal visits compared to controls. The FAS/FAE children had lower birth weights and higher rates of sibling deaths. The use of birth certificate data is a useful data source to compare maternal, paternal and prenatal characteristics for a population of children with FAS/FAE.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Addiction biology 1 (1996), S. 0 
    ISSN: 1369-1600
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recent clinical and experimental studies have demonstrated that the habitual consumption of large amounts of ethanol has deleterious effects on the kidney. A variety of tubular defects have been described in patients with chronic alcoholism. Evidence is emerging that tubular dysfunction has an important pathophysiological role in a wide range of electrolyte and acid-base disturbances commonly observed in these patients, and possibly in alcohol-induced bone disease. These renal abnormalities are often reversible, disappearing with abstinence. However, since 1990 a few cases of a syndrome of acute tubular necrosis due to binge drinking of ethanol in the absence of other evident nephrotoxic mechanisms, or in association with the use of nonsteroidal anti-inflammatory drugs, have been reported. A link between glomerulonephritis and alcoholism has become evident. IgA nephropathy has been demonstrated at autopsy in 64% of chronic alcoholics and, more recently, the association between alcoholism and postinfectious glomerulonephritis has been described. Structural and functional abnormalities of the kidney are reported with increasing frequency in the fetal alcohol syndrome seen in children who have been prenatally exposed to ethanol. In addition, over the last few years experimental studies in vitro or in animal models have provided information about the biochemical and molecular basis of alcohol-induced injury to kidney. It is hoped that future experimental and clinical research will provide us with a more comprehensive knowledge of the mechanisms of renal damage in alcohol misuse.
    Type of Medium: Electronic Resource
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