Repeated binge drinking can be a risk factor for the development of alcohol dependence. Deborah Finn, a Professor of Behavioral Neuroscience at Oregon Health & Science University and a Research Pharmacologist at the VA Portland Health Care System, USA and her colleagues wanted to determine whether repeated binge drinking produced different responses in the brains of male and female mice, as has been found in alcoholdependent mice tested during the withdrawal phase.
Their study published in Frontiers in Genetics suggests that gene expression in the nucleus accumbens, an area of the brain linked to addiction is affected differently by repeated binge drinking in males and females. They found that in female mice, genes associated with hormone signaling and immune function were affected by repeated binge drinking, whereas in males, genes associated with nerve signaling were affected.
Gene expression is the process where specific genes are activated to produce proteins for use by the cell, e.g. as building blocks for new tissues or hormones. Gene regulation governs the amount and timing of gene expression. The researchers analysed gene expression in the nucleus accumbens. Further analysis examined the likely overall effect the regulation and expression of these genes would have on males and females.
The researchers found significant regulation of 50 genes in male mice and 70 genes in female mice after 7 ethanol binges. Notably, 14 genes were regulated in both males and females, representing common targets to binge ethanol drinking. However, expression of 10 of these 14 genes was strongly dimorphic (were regulated in the opposite direction) and only 4 of the 14 genes were regulated in the same direction. The top 30 regulated genes by binge ethanol drinking for each sex differed markedly in the male and female mice, and this divergent neuroadaptive response in the nucleus accumbens could result in dysregulation of distinct biological pathways between the sexes.
"Our results suggested repeated binge drinking had a very different effect on the neuroadaptive responses of the nucleus accumbens in males and females, with different pathways being activated in each sex. Pathway analysis suggests hormone signaling and immune function were altered by binge drinking in females, whereas nerve signaling was a central target of binge drinking in males," Finn commented. The authors say that their findings have important implications for the treatment of alcohol addiction and emphasise the need to tailor individual pharmaceutical treatments for male and female patients.
Source: Binge Ethanol Drinking Produces Sexually Divergent and Distinct Changes in Nucleus Accumbens Signaling Cascades and Pathways in Adult C57BL/6J Mice. DA. Finn, Jet al. Frontiers in Genetics, 2018;