The findings, published in the journal Molecular Psychiatry, present a new model for identifying biomarkers that may indicate a person with PTSD is more likely to develop alcohol use disorder.
"Having PTSD significantly increases the risk of developing alcohol use disorder, as individuals use alcohol to cope with stress and anxiety," said study author Dean Kirson from the Scripps Research Institute in the US.
Yet the underlying biology of comorbid disorders is generally not well understood.
"We hope our new knowledge of sex-specific changes in the brain will help propel the development of more targeted treatments," Kirson added.
Alcohol abuse disorder is also common, affecting some 15 million people in the US.
Those with stress and anxiety disorders such as PTSD are not only more likely to abuse alcohol, but also have increased alcohol withdrawal symptoms and relapse risk.
For the study, the research team examined behaviour, sleep patterns, inflammatory immune responses and levels of a neurotransmitter known as GABA (short for gamma-Aminobutyric acid), which lowers anxiety and increases feelings of relaxation and is a common feature of alcohol dependence.
For both male and female rats, traumatic stress and alcohol exacerbated other behaviours common in PTSD, such as social avoidance startle reactions and defensive behaviour.
Those who were identified as "drinking-vulnerable" prior to trauma most strongly showed avoidance of trauma-reminiscent places.
However, the scientists noted key differences in how males and females behave following trauma and saw markedly different patterns of GABA signalling.
For example, males showed increased GABA receptor function, while females showed increased GABA release.
The team also found that males exhibited an immune-based biomarker--small protein known as cytokines, which are secreted by immune cells--that determined vulnerability to an alcohol use disorder. The females did not.
"We identified profiles of specific cytokines, many not previously linked to stress behaviours, that strongly related to poor drinking outcomes," the authors wrote "These may be important clinically or even mechanistically, but they were unique to males, so we have work ahead of us to find similar biomarkers for females," they noted.