A particularly salient effect of long-term cocaine exposure in postmortem brains we studied was alteration in the expression of genes involved in mitochondrial inner membrane functions and oxidative phosphorylation (Zhou et al., 2011). Interestingly, these genes integral to cellular energy production have also been implicated in neurodegenerative diseases (Cho, Nakamura, & Lipton, 2010). Among the 90 genes encoding components of oxidative phosphorylation whose expression could be reliably evaluated by RNA-Seq of hippocampal mRNA, 32 were differentially expressed (uncorrected P<0.05), and all were downregulated. Furthermore, 74 of the 90 genes (including the 32 genes that were significantly downregulated) displayed reduced expression levels in cocaine addicts. These findings were also highly consistent with previous brain imaging studies that have revealed negative effects of cocaine on brain glucose metabolism (London et al., 1990; Lyons, Friedman, Nader, & Porrino, 1996; Macey, Rice, Freedland, Whitlow, & Porrino, 2004; Thanos, Michaelides, Benveniste, Wang, & Volkow, 2008). Furthermore, alteration of certain genes encoding for mitochondrial components induced by cocaine (Lehrmann et al., 2003) and nicotine (Wang, Kim, Donovan, Becker, & Li, 2009) exposure had also been reported previously.
