Targeting the link between PTSD and alcohol use disorder

BioTechniques News
Aisha Al-Janabi

Individuals with post-traumatic stress disorder (PTSD) are more likely to develop alcohol use disorder (AUD). Now, meet the drugs that might be able to break this link.

Scientists at Scripps Research (CA, USA) have examined how certain drugs affect alcohol preference in rat models of PTSD, potentially offering a novel treatment for targeting both PTSD and AUD via a single brain pathway. In the United States, approximately 12 million adults have PTSD during any given year. Such a prevalent disorder has also been linked to AUD, meaning that people with PTSD are more likely to develop AUD.

Previous research has shown that a brain protein, FKBP5, is implicated in both PTSD and AUD; FKBP5 is involved in facilitating the stress response. FKBP5 variants have been linked to an increased risk of PTSD and AUD. This protein has led researchers to further investigate the brain pathways associated with both PTSD and AUD.

“The overlap of PTSD and AUD is a major problem,” commented co-senior author Marisa Roberto. “We’ve shown that there is potential to alleviate both disorders by targeting brain pathways that they share.”

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The current research team investigated the effects of FKBP5 inhibitors, an FDA-approved Parkinson’s treatment benztropine and the experimental drug SAFit2, on rat models displaying symptoms similar to those expressed in human comorbid PTSD and AUD. The rats underwent shock stress events and then voluntarily consumed alcohol. These rats were assessed for trauma-associated behaviors; researchers monitored their sleep cycles, hyperarousal, fear response and irritability.

They demonstrated that benztropine reduced alcohol preference in stressed rats and reduced aggressive behaviors in female rats, specifically. SAFit2 was found to reduce alcohol consumption in male rats, but not female rats; however, it did decrease fear response in both male and female rats. Neither drug affected rats’ sleep cycles.

“The results may have varied between male and female animals because of reproductive hormones,” said Bryan Cruz, co-first author. “There is new literature suggesting that the activity of these kinds of compounds varies in females throughout the estrous cycle.”

Due to benztropine’s current commercial use in treating Parkinson’s disease, the team is excited about its potential application in treating PTSD/AUD. This study is an important step forward in determining how FKBP5 proteins can be targeted to prevent AUD following PTSD onset. However, more research is needed to understand whether these FKBP5 inhibitor drugs could be used to prevent relapse of both PTSD symptoms and AUD.

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