Peripheral blood α-synuclein mRNA levels are elevated in cynomolgus monkeys that chronically self-administer ethanol

The gene SNCA (or NACP), which codes for α-synuclein, a small synaptic protein involved in dopaminergic neurotransmission, maps to a quantitative trait locus for alcohol preference and is differentially expressed in specific brain regions in alcohol-preferring versus -nonpreferring rats. Moreover, elevated α-synuclein messenger RNA (mRNA) and protein levels in peripheral blood have been shown to be associated with craving in patients with alcoholism. The focus of this study was to evaluate gene expression, including the levels of α-synuclein mRNA, in peripheral blood in nonhuman primates that were induced to drink ethanol (4 months) and then allowed 14 months of 22-h/day access to ethanol (4% wt/vol) or water compared to alcohol-naïve controls. Differential gene expression, including α-synuclein mRNA levels, was measured in 18 cynomolgus macaque monkeys, 8 that had been chronically self-administering ethanol for 18 months and 10 that were alcohol naïve. Cynomolgus monkeys in this study self-administered ethanol at average rates of between 1.2 and 4.2 g/kg/day. This group of ethanol-drinking monkeys had a highly significant 3.21-fold higher level of α-synuclein mRNA in peripheral blood than alcohol-naïve controls. These data agree with recent reports of elevated α-synuclein mRNA and protein in the blood of human alcoholics, support the concept of an association between α-synuclein and alcoholism, and demonstrate, for the first time, a biomarker present in rats, monkeys, and humans for the consumption of ethanol.