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Chunk #39 — 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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The reduced expression of 13 of 15 genes (Table 4) associated with Srebf1 (sterol regulatory element binding transcription factor 1) suggests reduced cholesterol and fatty acid synthesis (Ong et al., 2000; Tabernero et al., 2002), which is also consistent with excessive binge drinking having a negative impact on neuronal function. In addition, Srebf1, Hmgcr, and Hmgcs1 are all implicated in white matter integrity (e.g., Carter, 2007; Xiang et al., 2011), which is disrupted after chronic alcohol abuse (Harris et al., 2008). Neither the GO (Table 2) nor the KEGG (Table 3) analysis provided a clear answer on the effects of repeated excessive binge drinking on neuronal function in the VTA, since both positive (e.g., regulation of actin cytoskeleton and cell adhesion) and negative (e.g., killer cell mediated cytotoxicity, negative regulation of transcription, and steroid biosynthesis with all genes down-regulated) effects on cellular function are evident.