Biology may help explain why women are more vulnerable to alcohol’s long-term effects. New research from Scripps Research shows that female brains respond to alcohol earlier and more strongly than male brains — possibly long before dependence develops.
In a preclinical study published in Biological Psychiatry, researchers found that even low levels of alcohol altered how brain cells communicated in female rats, while the same changes only appeared in males after alcohol dependence had taken hold. The changes were observed in the brain’s noradrenergic system, which regulates stress, emotion and attention.
“This suggests that the female noradrenergic system may be more sensitive at baseline,” said co-first author Alexia Anjos-Santos, a visiting PhD candidate. “But additional research is needed to confirm and better understand this potential sex-based difference.”
The team also tested two FDA-approved medications that act on this system. Prazosin, an α1-receptor blocker, reduced alcohol consumption in both dependent and non-dependent female rats. Propranolol, a β-blocker, only worked once dependence had developed.
“Our results ... suggest that α1 receptor-specific medications like prazosin could help reduce alcohol cravings as well as stress-related symptoms like anxiety — even in people with milder patterns of alcohol use,” said senior author Marisa Roberto, PhD, a professor of neuroscience at Scripps.
To explore whether these findings could apply to people, the team examined postmortem brain tissue from women with and without alcohol use disorder. They found changes in related brain regions tied to stress and emotional regulation, adding support for sex-specific treatment strategies.
“Overall, our studies point to sex differences at the preclinical level ... that may very well contribute to differences in treatment efficacy at the clinical level,” Roberto said.
The researchers plan to continue exploring how stress-related medications might help reduce not just drinking, but also anxiety, depression and pain sensitivity — especially in the early stages of alcohol misuse.
This study was supported by the National Institutes of Health through multiple grants, as well as by the São Paulo Research Foundation.