Researchers have discovered that a chemical in the brain makes alcohol taste bitter to women and may explain the difference in drinking habits between the sexes. The discovery could pave the way for novel treatments to help women curb excessive alcohol use.
Globally, alcohol use contributes to around 3 million deaths annually. While previous studies have noted differences in alcohol misuse and dependence between men and women, newer research suggests that, over the last 20 years, there’s been an increase in risky drinking behaviors, such as binge drinking, in women.
On a molecular level, the neuropeptide protein cocaine- and amphetamine-regulated transcript (CART) has been implicated in a range of physiological and pathophysiological functions, including energy balance, depression, anxiety, and reward-related behaviors like alcohol use disorder. However, due to difficulties manipulating the CART system, it’s remained relatively understudied.
Researchers from The Florey Institute for Neuroscience and Mental Health in Melbourne, Australia, examined the CART system in an effort to explain the differences in drinking habits between the sexes and found that it comes down to the chemical’s effect on taste.
“The taste of alcohol is an important and often overlooked factor that drives alcohol preference, intake and use,” said Leigh Walker, corresponding author of the study. “We have identified a chemical in the brain that makes alcohol taste bitter to females unless the drink is sweetened.”
Male and female mice, including animals with the CART gene knocked out, were trained to consume high levels of alcohol (ethanol). They were then given continuous access to a bottle containing ethanol and one containing water for 10 weeks, and their intake was measured daily. To determine whether taste affected alcohol consumption in female mice, bottles of ethanol were then supplemented with sucrose.
“Alcohol has an underlying bitter taste,” Walker said. “When we inhibited CART in male mice, their drinking increased. And when we knocked out the same brain chemical in female mice, they drank less. But when the alcohol was sweetened, the female mice drank more. This tells us that without CART, alcohol is unpalatable to females.”
The researchers discovered that the differences they observed were not due to circulating levels of sex hormones but were related to a part of the brain where CART contributes to regulating alcohol consumption, the central nucleus of the amygdala (CeA). In mice where CeA CART has been neutralized, female mice consumed less plain but more sweetened alcohol.
They say their research has identified a novel mechanism by which CART mediates alcohol intake, specifically in female mice, by altering bitter taste sensitivity. It could pave the way for treatments designed to help women stop binge drinking or otherwise engaging in unhealthy drinking behaviors.
“If we can find a way in future to target the CART neuropeptide system, we may be able to create treatments to help women curb excessive alcohol use,” said Walker. “And if we can work out how male and female brains differ, it will open unprecedented opportunity to treat disorders of the brain in women, including alcohol use disorders.”
The study was published in the journal Neuropsychopharmacology.