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Obesity is associated with increased mineralocorticoid receptor (MR) activity in peripheral and possibly central tissues, decreased hippocampal size in humans, and impaired hippocampal learning in rodents. The MR is expressed in hippocampal neurons, and MR blockade improves hippocampal learning in obese animals. The goal of the study was to determine whether MR blockade would modulate paired\u2010associate learning in men and women with obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Men and women ages 20\u201061 years with BMI between 30\u201045 kg\/m<jats:sup>2<\/jats:sup> were randomly assigned to placebo (<jats:italic>n<\/jats:italic>\u2009=\u200911; 7 women) or 50 mg spironolactone daily (<jats:italic>n<\/jats:italic>\u2009=\u200912; 7 women) for six weeks. At baseline and post\u2010treatment, subjects underwent a clinical and hormonal evaluation. They also underwent a computerized task that assesses paired\u2010associate learning and has been shown by functional magnetic resonance imaging to activate the hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In an ANCOVA model that adjusted for baseline paired\u2010associate learning, age, and race, spironolactone treatment was associated with a significant (<jats:italic>P<\/jats:italic>\u2009=\u20090.043) improvement in hippocampal memory as compared to placebo treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings demonstrate, for the first time, that blocking MR with chronic, low\u2010dose spironolactone treatment improves paired\u2010associate learning in individuals with obesity, suggesting that MR activation contributes to hippocampal memory modulation in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.21104","type":"journal-article","created":{"date-parts":[[2015,5,9]],"date-time":"2015-05-09T11:01:26Z","timestamp":1431169286000},"page":"1136-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of mineralocorticoid receptor blockade on hippocampal\u2010dependent memory in adults with obesity"],"prefix":"10.1002","volume":"23","author":[{"given":"Lisa S.","family":"Rotenstein","sequence":"first","affiliation":[{"name":"Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Pediatrics Boston Children's Hospital Boston Massachusetts 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