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Ethanol abuse, alcoholism and the medical complications of excessive drinking are now major health problems worldwide. The alcohol dependence syndrome is characterised by tolerance and physical dependence ( the presence of a withdrawal syndrome). Ethanol withdrawal, in addition, to being a health hazard in itself, can act as a negative reinforcer to promote continued ethanol consumption. Alcohol dependence can be considered to result from adaptive changes produced by the chronic presence of etha ....Ethanol abuse, alcoholism and the medical complications of excessive drinking are now major health problems worldwide. The alcohol dependence syndrome is characterised by tolerance and physical dependence ( the presence of a withdrawal syndrome). Ethanol withdrawal, in addition, to being a health hazard in itself, can act as a negative reinforcer to promote continued ethanol consumption. Alcohol dependence can be considered to result from adaptive changes produced by the chronic presence of ethanol in the brain. In this research programme we will learn more about the adaptive changes in the NMDA receptors, the major excitatory receptors in the brain. Current psychopharmacologic management of human alcoholism is limited and suboptimal. We will explore the efficacy of drugs to control behaviours and withdrawal-induced brain cell death. Effective treatment of the syndrome is crucial since withdrawal induces changes, which increases the severity of subsequent withdrawal episodes and its associated brain damage. The outcomes of this research will be a better understand of the underlying changes involved in ethanol dependence and better therapies to ameliorate the withdrawal syndrome.Read moreRead less
Molecular Cell Biology Of HNP22: Role In Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$346,320.00
Summary
We used a differential screening procedure to detect changes in gene expression in the human alcoholic brain and described a novel gene, which we named hNP22, with increased expression in the superior frontal cortex of the alcoholic cases. This is the first report of a novel alcohol-responsive gene isolated from the human brain. We now propose to further explore the hNP22 gene, its product and its regulation in human brain tissue, and in a variety of experimental systems. We will determine how p ....We used a differential screening procedure to detect changes in gene expression in the human alcoholic brain and described a novel gene, which we named hNP22, with increased expression in the superior frontal cortex of the alcoholic cases. This is the first report of a novel alcohol-responsive gene isolated from the human brain. We now propose to further explore the hNP22 gene, its product and its regulation in human brain tissue, and in a variety of experimental systems. We will determine how protein expression correlates with the level of alcohol consumption. We will use animal and cell culture models to determine the response of the gene to various stimuli. We will express the recombinant protein to determine its function. It is likely that the gene product may be a component in an important signal pathway within neuronal cells and thus may represent a novel target for therapeutic intervention.Read moreRead less
Organic Brain Damage After Non-fatal Opioid Overdose
Funder
National Health and Medical Research Council
Funding Amount
$244,858.00
Summary
The study will provide the first data on the level and nature of brain damage due to opioid overdose. The extent to which overdose survivors suffer brain damage has important implications for clinical management, particularly in relation to behavioural problems. It will also provide the first data on brain damage and drug treatment performance. Screening of those with an overdose history may lead to specialised management of these individuals with the potential for improved treatment outcome.
Forebrain Neuroadaptations To Chronic Morphine Treatment
Funder
National Health and Medical Research Council
Funding Amount
$435,956.00
Summary
Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerv ....Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerve cells in the brain. The affected nerve cells are responsible for causing new behaviours that appear once addiction is established. Addiction is not exclusive to humans. Animals will self-inject the same addictive drugs that humans use, and show many other kinds of addictive behaviours that parallel aspects of human addiction. Studying the effects of addictive drugs on rats and other animals has been very important in working out where and how drugs work. We now have a very good idea of which parts of the brain are affected by drugs, and it turns out that most addictive drugs act in the same places. We also now know for all of the major drugs, exactly which parts of nerve cells they affect. However, this turns out to be only the first step as the nerve cells that directly respond to drugs can affect other whole networks of nerve cells. This study is going to look at how morphine, a drug that is related to heroin, affects nerve cells in a part of the brain that helps cause addiction. It is going to work out which of the many pathways in this brain region are affected by morphine treatments that cause addiction in rats. It will then see what is happening to single nerve cells in the affected pathways. If we can understand more about these processes it may become possible to come up with new ways to treat addiction. We will also understand much more about the production of powerful emotional and behavioural drives so many of us find hard to control.Read moreRead less