Featured Paper of the Month – February 2023
Published in Molecular Psychiatry with authors from the NIDA IRP Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section and Neurobiology of Addiction Section.
The steroid hormone aldosterone regulates fluid and electrolyte homeostasis mainly via its mineralocorticoid receptor. Previous studies suggest that this pathway may also modulate alcohol seeking and consumption. Spironolactone is a nonselective mineralocorticoid receptor antagonist primarily used in clinical practice to treat cardiovascular conditions. Preliminary evidence indicates that spironolactone may also reduce alcohol use. In this study, we first tested spironolactone in a mouse model of alcohol binge drinking and found that spironolactone dose-dependently reduced alcohol drinking. Using a model of alcohol dependence, we also found that spironolactone reduced alcohol self-administration in rats. Finally, in a large pharmacoepidemiologic cohort study, people who received spironolactone for conditions unrelated to alcohol drinking showed reduced alcohol consumption, compared to propensity score-matched individuals who did not receive spironolactone. This reduction in alcohol use was greater among heavy-drinking individuals and those who received higher doses of spironolactone. These convergent findings across three species indicate that spironolactone may be repurposed and further studied as a novel pharmacotherapy for alcohol use disorder.
In: Mol Psychiatry, vol. 27, no. 11, pp. 4642–4652, 2022, ISSN: 1476-5578.