A new study linking the hormone aldosterone with risk for alcohol use disorder (AUD) may present a new avenue for developing medication treatment for AUD. “We believe that this target might be particularly promising for those individuals who drink excessive amounts of alcohol to cut their stress and anxiety,” senior author Lorenzo Leggio, M.D., Ph.D., chief of the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIAAA, told Medscape Medical News.

The 2017 study, conducted in collaboration with a team of investigators in the United States and Europe, found that aldosterone, a hormone produced in the adrenal glands, may be a contributing factor in AUD. Aldosterone binds to mineralocorticoid receptors (MRs) and helps regulate electrolytes, fluid balance, and blood pressure. MRs are located throughout the body and are present in two key regions of the brain involved in developing and maintaining AUD: the prefrontal cortex and the amygdala, which play a role in stress, impulsivity, decision-making and excessive alcohol drinking.

Previous studies, including a 2008 pilot study done by Leggio and colleagues, found that alcohol-dependent patients with higher blood aldosterone concentrations have higher alcohol craving. The new research, published in Molecular Psychiatry, found evidence further supporting the role of aldosterone in AUD via its MR receptor. This neuroendocrine pathway may be particularly important in anxiety, stress and stress-induced alcohol drinking.

Three separate studies were conducted as part of the new research: one in humans, the other two in animals.

A study with non-human primates found that the animals who self-administered alcohol daily for six to twelve months had significantly higher aldosterone concentrations, compared to their levels of aldosterone prior to alcohol administration. The researchers also found that the lower the MR gene expression in the amygdala, the more the animals drank.

Similar results were found in the amygdala of alcohol-dependent rats. Additionally, there was an increase in anxiety-like behavior and compulsive drinking in rats with lower levels of MR gene expression in their amygdala. Conversely, decreased anxiety and lower levels of compulsive drinking were associated with higher levels of MR gene expression in the amygdala, suggesting that higher MR expression may be a protective factor against compulsive drinking, or lower levels of MR gene expression may increase vulnerability for anxiety-related compulsive drinking in the rat AUD model.

Researchers also conducted a human study with about 40 individuals who were in treatment for AUD. In these participants, they found higher blood aldosterone concentrations in those who continued drinking during the 12-week period, compared with those who were abstinent during that time period. The researchers found that alcohol-dependent patients with higher blood concentrations of aldosterone also had higher craving for alcohol, higher anxiety and consumed more alcohol.

The findings from the three studies provide support for a relationship between alcohol misuse, AUD, and specific changes in the aldosterone/MR pathway marked by increased circulating aldosterone and decreased mineralocorticoid receptor gene expression in the amygdala. These findings highlight the role of neuroendocrine mechanisms in AUD and their potential use for future development of pharmacotherapies for AUD.

“This study is an initial step towards a better understanding of the role of aldosterone and its MR receptor in alcohol drinking,” said Leggio in an interview with MedicalResearch.com. “It is now important to investigate the potential causality link by conducting preclinical studies and then, if appropriate, clinical studies with the ultimate goal of investigating whether this initial information may eventually lead to better treatments for our patients with alcohol use disorder.”