The neurotransmitter disturbances which occur during alcoholism and chronic alcohol use are not well understood. Although various neuroadaptive mechanisms have been inferred from model experiments in animals, the relevance of these mechanisms to human alcoholism is not well-established. One method to test hypotheses of neurotransmitter disturbance is to assess the expression of genes involved in neurotransmission in post mortem specimens of specific regions of the human brain by in situ hybridization of mRNA. This technique has the advantage of providing very specific information about the expression of specific genes which animal and clinical research have targeted as affected in alcoholism. However, the technique also requires that the mRNA in the post mortem specimens not be degraded by non-specific factors, including the debilitation produced by alcohol abuse itself.
The first aim of this study is to obtain post mortem brain tissue from 40 alcoholics and 40 normals and to analyze the mRNA content and integrity. The data will be analyzed to determine if non-specific factors, related to alcohol use or to the events surrounding death and autopsy, influence mRNA content and integrity.
The second aim i s to examine the expression of genes related to GABA-A receptors, including the gamma-2-L component, which conveys sensitivity to alcohol.
The third aim i s to examine the expression of beta adrenergic receptors, which have also been linked to the response to alcohol. This component will thus support investigations in humans of neurobiological and molecular biological mechanisms that are also the focus of research in animal models in other Center projects.
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