As part of the study researchers conducted experiments on mice to see the neuro-toxic effects of alcohol withdrawal by examining four groups of selectively bred mice: two female groups, including one prone to severe withdrawal and one resistant to severe withdrawal, and two similar male groups. Four control groups also were used.
Researchers used DNA microarray or 'gene chip' analysis, and examined 5,000 genes from the prefrontal cortex, the area of the brain implicated in complex planning, personality expression and social behaviour, and is involved in withdrawal-related brain circuitry.
They then identified a total of 295 alcohol-regulated genes for each mouse group.
"We're interested in that part of the brain because it's important in inhibitory control. Alcoholics are unable to display good inhibitory control," Wiren said.
Researchers examined cells in the lateral parietal cortex area, which is part of the network of brain regions, in addition to the prefrontal cortex, involved in inhibitory control, ten days after alcohol withdrawal, and identified live and dead cells with tissue stains.
The study found that female mice were more susceptible to neurotoxic effects of alcohol withdrawal, including significantly increased brain cell death, than male mice. It also found the gender difference exists whether the animals were prone to severe withdrawal due to a genetic predisposition, or resistant to it.
"At this one time point, which is the peak for cell death, we clearly see females are showing enhanced brain damage compared to the males. So, if you're female, the cells are dying; if you're a male, the cells are not," Wiren said.
Researchers noted that such brain damage might underlie debilitating cognitive dysfunction and motor deficits observed in some alcoholics. In addition, disruption of inhibitory functions in the prefrontal cortex might contribute to excessive drinking and the self-sustaining nature of alcoholism.
The findings of the study were published in the online edition of the journal Neuropsychopharmacology.