Glutamate - Adenosine Interactions And Drug-seeking
Funder
National Health and Medical Research Council
Funding Amount
$558,046.00
Summary
Substance abuse is a significant social and economic burdern upon Australian societies and on societies around the world. Treatment remains problematic due to the multi-layer nature of the disease, difficulties with treatment compliance and less than ideal treatment regimes. The present study aims to improve treatments for alcohol and drug abuse using a polypharmacy or multiple therapy approach, using pre-clinical models to determine the utility of this approach.
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
Cortictropin Releasing Factor As A Therapeutic Target For Alcohol And Drug Abuse
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
A key problem with alcoholism, as with addiction generally, is the chronically relapsing nature of the disorder. This can be modelled in rodents and there is good general correspondence between animal studies of reinstatement and human experience of relapse. We have identified brain chemicals involved in this process. Consequently, by better understanding the biological mechanisms related to addiction and relapse, we will be in a position to counter this devastating condition.
Molecular Pathogenesis Of Amino Acid Neurotransmission In Human Chronic Alcoholism
Funder
National Health and Medical Research Council
Funding Amount
$378,750.00
Summary
Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain, and may selectively affect certain specific functions of nerve cells. It appears that alcoholism affects processes which control the excitability in discrete regions of the brain, and hence can cause them to be over-stimulated. It is known that if brain cells are excessively stimulated for long periods, they are in danger of being killed. This study will determine how the tissue s capacity to proce ....Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain, and may selectively affect certain specific functions of nerve cells. It appears that alcoholism affects processes which control the excitability in discrete regions of the brain, and hence can cause them to be over-stimulated. It is known that if brain cells are excessively stimulated for long periods, they are in danger of being killed. This study will determine how the tissue s capacity to process glutamate, the brain s major natural excitant, is altered in the regions which are selectively damaged in alcoholics. How these processes are affected by heredity, and by diseases commonly associated with alcoholism such as cirrhosis of the liver, will also be explored. An understanding of how selective brain damage occurs in alcoholics will help us to devise new drug therapies to combat and prevent it. As well, selective brain damage is found in a great many neurological diseases, so this study will provide a model which may help to dene general processes which give rise to localised neurological damageRead moreRead less