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Chunk #51 — Discussion

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Changes in gene expression within the ventral tegmental area following repeated excessive binge-like alcohol drinking by alcohol-preferring (P) rats.
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In summary, the overall results of the bioinformatic analyses (Table 8) indicated the up-regulation of a number of genes that could produce a pro-inflammatory response, promote excitotoxic neuronal damage, and increase protein degradation. These results suggest that the high BECs repeatedly attained in the present study could be causing neuronal damage in the VTA. Consistent with this interpretation are the findings that several genes involved in cholesterol and fatty acid synthesis were down-regulated (Table 8). Also, alterations in expression of genes around 3 transcription factors suggested reduced excitation-coupled transcription. Thus, the combination of alterations in transcription factors, metabolism of proteins and steroid, and pro-inflammatory response are indicators that this level of alcohol drinking may be repeatedly producing brain ethanol levels that could cause cellular damage.