Mitochondria also participate in alcohol metabolism by converting acetaldehyde into acetate (Manzo-Avalos and Saavedra-Molina, 2010). An RNA-seq study found 56 genes involved in mitochondrial function that were differentially expressed in postmortem frontal cortex of alcoholic subjects (Zhang et al., 2014a). Additionally, previous microarray studies of human alcoholic brain tissue have shown differential expression of genes related to mitochondrial function (Liu et al., 2006). Therefore, it can be hypothesized that the differential expression of genes related to alcohol metabolism (e.g. ADH, ALDH, P450) in brain could alter the reinforcing effects of alcohol and change drinking behavior. This hypothesis was supported by injecting lentiviral vectors (anti-catalase shRNA or rADH1), which inhibit catalase synthesis or increase activity of ADH, respectively (Karahanian et al., 2011). Administration of the anti-catalase lentiviral vector into the ventral tegmental area significantly reduced ethanol consumption and ethanol-stimulated dopamine release in the nucleus accumbens shell; whereas, the rADH1-encoding vector facilitated an increase in ethanol intake (Karahanian et al., 2011). This study reinforces the key role of metabolism in chronic alcohol consumption and demonstrates how network-wide changes in differential expression of genes important in alcohol metabolism can significantly alter drinking behavior.
