Changes in gene expression within the ventral tegmental area following repeated excessive binge-like alcohol drinking by alcohol-preferring (P) rats.

摘要: Abstract The objective of this study was to detect changes in gene expression the ventral tegmental area (VTA) following repeated excessive binge-like (‘loss-of-control') alcohol drinking by alcohol-preferring (P) rats. Adult female P rats ( n  = 7) were given concurrent access 10, 20, and 30% EtOH for 4 1-h sessions daily 10 weeks followed 2 cycles abstinence access. Rats sacrificed decapitation 3 h after 4th EtOH-access session at end second 2-week relapse period. A water-control group  = 8) also sacrificed. RNA prepared from micro-punch samples VTA individual rats; analyses conducted with Affymetrix Rat 230.2 GeneChips. Ethanol intakes 1.2–1.7 g/kg per session, resulting blood levels >200 mg% session. There 211 unique named genes that significantly differed (FDR = 0.1) between water groups. Bioinformatics indicated alterations a) transcription factors reduced excitation-coupled promoted excitotoxic neuronal damage involving clusters associated Nfkbia , Fos Srebf1 b) cholesterol fatty acid synthesis, increased protein degradation, c) involved cell-to-cell interactions regulation actin cytoskeleton. Among genes, there 62 showed differences alcohol-naive non-preferring (NP) rats, 43 changing toward NP-like These are a pro-inflammatory response, enhanced response glucocorticoids steroid hormones. Overall, results indicate can change may alter function several ways, some which be deleterious.