Alcohol consumption

The presence of the Bmal1 gene in part of the forebrain has opposite effects on ethanol consumption in men and women

It’s a question often heard after the New Year: “Why do we drink the way we do?” A group of researchers has found that at least some of this is linked to a particular protein in the part of the forebrain that regulates decision-making and the perception of rewards, among other things.

This is the subject of a recent article in the journal Nature. Communications Biology. In it, the researchers announce that the presence of the Bmal1 The gene in the striatum affects alcohol consumption in both male and female mice – but in a sexually dimorphic way. Male mice without protein consumed more alcohol than those that had it, while female mice without protein consumed less than females with it.

Bmal1 is also an integral part of the suprachiasmatic nucleus, the master circadian clock found in all mammals that regulates the sleep-wake cycle. Previous association analyzes of clock genes have revealed a potential role for Bmal1 in drinking behavior. Expanding on this – and considering gender differences in alcohol consumption and in certain functions of clock genes – the researchers hypothesized that Bmal1 may affect alcohol consumption in a gender-dependent manner.

The study was led by Nuria de Zavalia, research associate and lab manager at the Center for Studies in Behavioral Neurobiology and supervised by Shimon Amir, professor of psychology and university research professor emeritus. Co-authors are research associate Konrad Schoettner, undergraduate student Jory Goldsmith, research assistant Pavel Solis, alumna Sarah Ferraro (PhD 21), and research assistant Gabrielle Parent.

Risk in women, protection in men

The researchers created two strains of mice, using molecular biology methods to suppress or “knock out” the Bmal1 striatal medium spiny neuron gene in one of them. The gene remained present in other parts of the body, as it plays an essential role in the circadian clock. The other line was used as a control.

The men who had the Bmal1 gene deleted from the striatum were found to consume more alcohol than those who did not delete it, while in women the results were the opposite: those without Bmal1 consumed less alcohol than those who drank it. (Normally, female rodents tend to consume more alcohol per body weight than males.)

“The main conclusion we can draw is that in women, Bmal1 in the striatum confers risk, because they consume more alcohol when the gene is present,” says Amir. “In men, the gene is protective, because they drink less alcohol. The sex differences you see in normal mice are eliminated when the gene is removed from the striatum.”

Amir notes that neither sugar consumption nor circadian rhythms are affected by the gene deletion.

“It seems like streaked Bmal1 plays a causal role in controlling alcohol consumption and makes an important contribution to gender differences in alcohol consumption,” he explains.

A basis for gender-based treatment?

Researchers believe this discovery may help treat addiction in humans. For example, while women report lower alcohol use and dependence than men, they suffer more from the harmful consequences of alcohol use and dependence.

“So far, limited biological and pharmacological treatments for alcohol dependence do not discriminate between males and females, even though there are major differences in drinking behavior and dependence. gender,” he said. “By uncovering mechanisms of sex dimorphism, addiction treatment specialists could ultimately use this knowledge to develop sex-based treatment.”

This work was supported by grants from the Canadian Institutes of Health Research.

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Materials provided by Concordia University. Original written by Patrick Lejtenyi. Note: Content may be edited for style and length.