humans, it usually denotes many years of heavy use. This one fact appears to explain most of the differences observed in studies of rodents versus those on people. More widespread and divergent molecular and cellular changes have been observed in the chronically addicted human postmortem brain. In a study of postmortem prefrontal cortex from chronic cocaine abusers, Lehrmann and colleagues found expression alterations in multiple cellular functional domains, including energy metabolism, mitochondrial oxidative phosphorylation, oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity (Lehrmann et al., 2003). Interestingly, they also noted two distinctive states of transcription regulation, an elevated gene expression profile in the recent active cocaine abusers and decreased expression state in the non-active abusers. Altered expression in cocaine addicts has also been shown in myelin-related genes. In a study by Albertson and colleagues (Albertson et al., 2004; Bannon et al., 2005) on human postmortem NAc, the most prominent changes were decreases of myelin basic protein (MBP), proteolipid protein, and myelin-associated oligodendrocyte basic protein. The expression changes were also consistent with a decrease in the number of MBP-immunoactive oligodendrocytes. A study by Mash and colleagues also found cocaine-induced expression changes in genes involved in regulating extracellular matrix integrity and
