Ethanol-Responsive Brain Region Expression Networks: Implications for Behavioral Responses to Acute Ethanol in DBA/2J versus C57BL/6J Mice

摘要: Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial molecular basis for adaptive behaviors addiction. The inbred mouse strains DBA/2J C57BL/6J exhibit contrasting behavioral responses ethanol. We used oligonucleotide microarrays bioinformatics methods characterize patterns three brain regions these strains. Expression profiling included examination both differences 4 h after saline injection or (2 g/kg). Using a rigorous stepwise method microarray analysis, we identified 788 genes differentially expressed control versus mice 307 ethanol-regulated nucleus accumbens, prefrontal cortex, ventral tegmental area. There were strikingly divergent ethanol-responsive two Ethanol-responsive also showed clustering at discrete chromosomal regions, suggesting local chromatin effects regulation. Ethanol-regulated generally related neuroplasticity, but regulation functional groups pathways was region specific: glucocorticoid signaling, neurogenesis, myelination cortex; neuropeptide signaling developmental genes, including factor Bdnf, accumbens; retinoic acid Bioinformatics analysis several potential candidate quantitative trait loci linked behaviors, further supporting role identifying complex traits. Brain region-specific neuronal plasticity may critical components development lasting phenotypes such as dependence, sensitization, craving.