Survivors of abuse and trauma are considerably more likely than other individuals to develop alcohol use disorder (AUD); according to some estimates, up to three-quarters of persons with PTSD have drinking problems. Scripps Researchers have identified a class of drugs that may be capable of breaking this link. The medicine decreased alcohol craving and consumption in PTSD animal models, as well as other PTSD-related features including aggressiveness, excessive fear, and hyperarousal. The findings were reported in the journal Neuropsychopharmacology.
“The overlap of PTSD and AUD is a major problem,” says co-senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine and a professor of Neuroscience at Scripps Research. “We’ve shown that there is potential to alleviate both disorders by targeting brain pathways that they share.”
According to the United States Department of Veterans Affairs’ National Center for PTSD, roughly 12 million individuals in the United States suffer with PTSD in any given year. Men and women with PTSD are more than twice as likely as the general population to misuse or become dependent on alcohol at some time in their life. Furthermore, those with both PTSD and AUD are more likely to have suicidal thoughts and engage in excessive violence than people with just one of the diseases.
According to studies, FKBP5, a protein located in the brain, has been related to both disorders. The FKBP5 gene regulates the brain’s stress response pathways, and genetic variations of the gene have been associated to an increased risk of AUD and PTSD. Higher levels of FKBP5 in animals have been linked to both stress and alcohol exposure. Bryan Cruz, PhD, and Valentina Vozella, PhD, co-first authors, investigated rats displaying symptoms comparable to comorbid human PTSD and AUD. The animals, like people with the disorders, drink more alcohol than the average person, are angry and fearful, and have anxiety and sleep problems, the researchers observed.
The rats were given either benztropine (Cogentin), an FDA-approved Parkinson’s disease treatment that targets many molecules in the brain, or SAFit2, an investigational chemical developed specifically to disrupt FKBP5.
They discovered that benztropine decreased alcohol desire and aggressive behaviour in stressed male and female animals. SAFit2 reduced alcohol consumption in stressed males and lowered intense fear in both males and females. Neither medicine interfered with sleep.
“The results may have varied between male and female animals because of reproductive hormones,” says Cruz. “There is new literature suggesting that the activity of these kinds of compounds varies in females throughout the oestrous cycle.”
According to the researchers, the fact that benztropine is currently FDA-approved shows the possibility of repurposing it in persons suffering from PTSD.
“We think FKBP5 inhibitors might be useful in preventing AUD after the onset of PTSD,” adds co-senior author Eric Zorrilla, PhD, associate professor in the Department of Molecular Medicine. “More work is needed to determine whether these compounds also can prevent the recurrent relapse that hampers recovery.”
