Risk in females, protection in males
The researchers created two lines of mice, using molecular biology methods to delete or “knock out” the Bmal1 gene from the striatum’s medium spiny neurons in one of them. The gene remained present in other parts of the body, since it plays a critical role in the circadian clock. The other line was used as a control.
Males who had the Bmal1 gene deleted from the striatum were found to consume more alcohol than the ones that did not have it deleted, while in the females, the results were the opposite: those without Bmal1 consumed less alcohol than those that had it. (Normally, female rodents tend to consume more alcohol per body weight than males.)
“The main conclusion we can draw from this is that in females, Bmal1 in the striatum confers risk, since they consume more alcohol when the gene is present,” Amir says. “In males, the gene is protective, as they drink less alcohol. The sex differences you see in normal mice are eliminated when the gene is taken out of the striatum.”
Amir notes that neither the sugar consumption nor circadian rhythms is affected by the deletion of the gene.
“It seems that striatal Bmal1 plays a causal role in the control of alcohol consumption and makes an important contribution to sex differences in alcohol intake,” he explains.