Neurogenetic studies of alcohol addiction

Crabbe, John C.

doi:10.1098/rstb.2008.0101

Cited by 51 publications

(52 citation statements)

References 120 publications

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“…T is generally recognized that studies on genetically tractable model organisms can provide information that is relevant for human disorders (Bilen and Bonini 2005;Mackay and Anholt 2006;Crabbe 2008;Flinn et al 2008;Woodruff-Pak 2008). Nonetheless, attempts to identify risk alleles for human diseases have relied almost exclusively on linkage studies in human families or association analyses in human populations without reliance on translational approaches based on model systems.…”

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confidence: 99%

Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics

et al. 2009

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Identification of risk alleles for human behavioral disorders through genomewide association studies (GWAS) has been hampered by a daunting multiple testing problem. This problem can be circumvented for some phenotypes by combining genomewide studies in model organisms with subsequent candidate gene association analyses in human populations. Here, we characterized genetic networks that underlie the response to ethanol exposure in Drosophila melanogaster by measuring ethanol knockdown time in 40 wildderived inbred Drosophila lines. We associated phenotypic variation in ethanol responses with genomewide variation in gene expression and identified modules of correlated transcripts associated with a first and second exposure to ethanol vapors as well as the induction of tolerance. We validated the computational networks and assessed their robustness by transposon-mediated disruption of focal genes within modules in a laboratory inbred strain, followed by measurements of transcript abundance of connected genes within the module. Many genes within the modules have human orthologs, which provides a stepping stone for the identification of candidate genes associated with alcohol drinking behavior in human populations. We demonstrated the potential of this translational approach by identifying seven intronic single nucleotide polymorphisms of the Malic Enzyme 1 (ME1) gene that are associated with cocktail drinking in 1687 individuals of the Framingham Offspring cohort, implicating that variation in levels of cytoplasmic malic enzyme may contribute to variation in alcohol consumption.

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confidence: 99%

Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics

et al. 2009

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“…This implies that pharmacotherapies for addictive substances which are commonly co-abused, like nicotine and ethanol must be evaluated in concert as well as separately [64]. In addition, research into the inter-relationship between genetics, environment and addictive substance or behaviour is crucial if successful pharmacotherapies are to be developed [55,65].…”

Section: Neuroethics Of Addiction Research and Treatmentmentioning

confidence: 99%

The Neuroethics of Pleasure and Addiction in Public Health Strategies Moving Beyond Harm Reduction: Funding the Creation of Non-Addictive Drugs and Taxonomies of Pleasure

Mackenzie

2010

Neuroethics

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We are unlikely to stop seeking pleasure, as this would prejudice our health and well-being. Yet many psychoactive substances providing pleasure are outlawed as illicit recreational drugs, despite the fact that only some of them are addictive to some people. Efforts to redress their prohibition, or to reform legislation so that penalties are proportionate to harm have largely failed. Yet, if choices over seeking pleasure are ethical insofar as they avoid harm to oneself or others, public health strategies should foster ethical choice by moving beyond current risk management practices embodied in the harm reduction movement. The neuroscience of pleasure has much to offer neuroethics and public health strategies. Distinguishing between 'wanting' and 'liking' fosters new understandings of addiction. These hold promise for directing the search for pharmacotherapies which prevent addiction and relapse or disrupt associated neuromechanisms. They could inform new research into creating lawful psychoactive substances which give us pleasure without provoking addiction. As the health and well being of human and other animals rests upon the experience of pleasure, this would be an ethical objective within public health strategy. Were ethical and neurobiological obstacles to ending addiction to be overcome, problems associated with excessive consumption, the lure of unlawful psychoactive substances and the paucity of lawful means to achieve pleasurable altered states would remain. Nonaddictive designer drugs, which reliably provided lawful access to pleasures and altered states, would ameliorate these public health concerns insofar as they fostered citizens' informed, ethical choices according to a neurobiological taxonomy of pleasures.

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“…Most diagnostic criteria of alcoholism are behavioural, including failure to control drinking quantity and frequency and continuation with knowledge of the social and medical consequences. It has been argued that there is no rodent model that resembles human alcoholism in all important aspects (26) . However, the power of rodent genetics allows a focus on the genetic basis of specific behavioural traits (26) .…”

Section: Alcohol-related Brain Gene Expression In Animal Modelsmentioning

confidence: 99%

“…It has been argued that there is no rodent model that resembles human alcoholism in all important aspects (26) . However, the power of rodent genetics allows a focus on the genetic basis of specific behavioural traits (26) . Several rodent strains have been selected for display of particular alcohol-related behaviours and then used to identify candidate genes associated with these behaviours.…”

Section: Alcohol-related Brain Gene Expression In Animal Modelsmentioning

confidence: 99%

The effect of alcohol and nicotine abuse on gene expression in the brain

Flatscher-Bader

Wilce

2009

Nutr. Res. Rev.

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Alcohol intake at levels posing an acute heath risk is common amongst teenagers. Alcohol abuse is the second most common mental disorder worldwide. The incidence of smoking is decreasing in the Western world but increasing in developing countries and is the leading cause of preventable death worldwide. Considering the longstanding history of alcohol and tobacco consumption in human societies, it might be surprising that the molecular mechanisms underlying alcohol and smoking dependence are still incompletely understood. Effective treatments against the risk of relapse are lacking. Drugs of abuse exert their effect manipulating the dopaminergic mesocorticolimbic system. In this brain region, alcohol has many potential targets including membranes and several ion channels, while other drugs, for example nicotine, act via specific receptors or binding proteins. Repeated consumption of drugs of abuse mediates adaptive changes within this region, resulting in addiction. The high incidence of alcohol and nicotine co-abuse complicates analysis of the molecular basis of the disease. Gene expression profiling is a useful approach to explore novel drug targets in the brain. Several groups have utilised this technology to reveal drug-sensitive pathways in the mesocorticolimbic system of animal models and in human subjects. These studies are the focus of the present review.

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Neurogenetic studies of alcohol addiction

Cited by 51 publications

References 120 publications

Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics

Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics

The Neuroethics of Pleasure and Addiction in Public Health Strategies Moving Beyond Harm Reduction: Funding the Creation of Non-Addictive Drugs and Taxonomies of Pleasure

The effect of alcohol and nicotine abuse on gene expression in the brain

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