Altered Monoamine Oxidase Gene Expression in Response to Alcohol Exposure
Many drugs of abuse have been shown to induce positive motivational states by increasing extracellular dopamine (DA) concentrations in the mesolimbic system. However, drugs such as alcohol also result in a subsequent DA depletion in the nucleus accumbens, which promotes alcohol re-administration in order to restore extracellular DA levels. This addictive potential of alcohol is contributed to by cellular changes in gene-expression, however there is no clear consensus regarding the mechanisms by which alcohol exerts its major neurobiochemical and behavioural responses.
Monoamine Oxidases (MAO) are mitochondrial enzymes responsible for the oxidative degradation of many neurotransmitters, including DA, serotonin and noradrenalin. We have used SH-SY5Y cell culture and quantitative real-time PCR to investigate transcriptional regulation of both MAO isoforms (MAO-A and MAO-B) in response to alcohol exposure. Our experiments show that exposure to alcohol causes immediate transcriptional up-regulation of MAO-A and a delayed transcriptional up-regulation of MAO-B. These data indicate that each isoform is under differential regulation at the transcriptional level, and suggest that changes in MAO gene expression may be associated with alcohol-induced neurobiochemical changes underlying alcohol addiction. These findings highlight a possible alternate avenue for alcoholism therapy through the use of monoamine oxidase inhibitors.