To examine gene expression changes related to alcohol-drinking behavior, we also performed hippocampal transcriptome analysis in P and NP rats (Fig. 10.2C) using RNA-sequencing (Zhou et al., 2013). The results indicated an overall pattern of altered expression of genes involved in neural development and synaptic functions. A total of 485 genes were differentially expressed at FDR<0.05 following correction for genome-wide testing. Differentially expressed genes were significantly enriched with segregating SNPs located in the coding regions and UTRs, indicating the potential involvement of cis-regulatory elements in these genes. Using functional annotation analysis with twofold enrichment as a cutoff, we identified several functional domains among the 485 differentially expressed genes, including calmodulin binding, synapse, and neuronal projection. Of particular interest was overrepresentation of the genes that function in glutamate, GABA, opioid, cholinergic, and adrenergic transmission (Fig. 10.2C). This pattern was consistent with the loss of mGluR2 receptor in P rats, but also more readily points to overall neuronal differences between P and NP rats that influence alcohol-drinking behaviors. The gene expression differences between P and NP rats are thus consistent and convergent
