Summary: This is the first description of the relationship between chronic ethanol self-administration and the brain transcriptome in a non-human primate (rhesus macaque). Twenty nine male animals self-administered ethanol on a daily basis for over 12 months. Gene transcription was quantified with RNA-Seq in the cortical Area 32. We constructed coexpression and cosplicing networks, and we identified areas of preservation and areas of differentiation between regions and network types. Correlations between intake and transcription included largely distinct gene sets and annotation categories across brain regions and between expression and splicing; positive and negative correlationswere also associated with distinct annotation groups. Our cosplicing analysis further identified the genes affected only at the exon inclusion level. In the Area 32 coexpression network, we identified a distinct hub set that included Ppp3r1 and Myeov2. Overall, the data illustrate that excessive ethanol self-administration is associated with broad expression and splicing mechanisms that involve membrane and synapse genes.
Overall Design: Thirty one samples of Rhesus Macaques that were experimentally naïve at the onset of alcohol induction (Macaca mulatta, n = 31, 4-11 years, 6-8 kg), were first induced to drink 4% (w/v) ethanol and then allowed to self-administer ethanol for over 12 months under open access conditions (22h/d, 7d/wk) with concurrent meals and continuous access to water. We then removed one outlier resulting in 30 samples presented here.
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