One strength of our study is that the same RNA-Seq method was used in both human and rat postmortem samples and therefore comparisons of relative gene expression levels across humans and across rats were valid. RNA-Seq has a large dynamic range of expression levels over which transcripts can be detected unlike DNA microarrays that lack sensitivity for genes expressing at low or high levels [21]. One caveat for our study is that the results may be confined to the hippocampus since gene expression is likely to vary across brain regions [59]. Finally, the aim of this study was to detect both overlapping and specific changes in gene expression in cocaine addicts and alcoholics. Therefore we did not automatically perform expression analyses for each gene across all 3 groups (2df). Instead we based our analysis for each gene on the plots shown in Figures 1, 2 and 3 and as indicated in Table 2. It could be argued that our FDR correction should have been greater than for 25 analyses. Nevertheless, the fact that this exploratory approach yielded results in humans that were congruent with results in rats suggests that our significant findings are not likely to be false positives.
