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Leptin administration significantly reduced immobility, a putative measure of behavioral despair, in the forced swim test in intact female mice in the proestrus phase but not in the diestrus phase of the estrous cycle. Moreover, leptin administration stimulated Akt phosphorylation in the hippocampus of female mice in proestrus but not in diestrus, in correlation with its differential behavioral effects in these two phases of the cycle. Leptin-induced behavioral responses and stimulation of hippocampal Akt phosphorylation in female mice were abolished by ovariectomy. By contrast, the antidepressant-like effect of leptin in male mice was not affected by gonadectomy (castration). Pretreatment with 17\u03b2-estradiol restored sensitivity to the effects of leptin on behavior and hippocampal Akt phosphorylation in ovariectomized female mice. These results suggest leptin regulates depression-like behavior and hippocampal Akt signaling in a sex-specific and estrous cycle-dependent manner.<\/jats:p>","DOI":"10.1210\/en.2015-1029","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T17:01:02Z","timestamp":1437066062000},"page":"3695-3705","source":"Crossref","is-referenced-by-count":25,"title":["Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin"],"prefix":"10.1210","volume":"156","author":[{"given":"Nicole","family":"Carrier","sequence":"first","affiliation":[{"name":"Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuezhen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"},{"name":"Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linshan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"},{"name":"Institute for Metabolic and Neuropsychiatric Disorders (X.W., L.S.), Binzhou Medical University, Yantai 256603, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Yun","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pharmacology (N.C., X.W., L.S., X.-Y.L.), The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2015,7,16]]},"reference":[{"issue":"2","key":"2020071612021034300_B1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1001\/archpsyc.60.2.184","article-title":"Screening for serious mental illness in the general population","volume":"60","author":"Kessler","year":"2003","journal-title":"Arch Gen Psychiatry"},{"issue":"1","key":"2020071612021034300_B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-0327(99)00158-5","article-title":"Gender differences in chronic major and double depression","volume":"60","author":"Kornstein","year":"2000","journal-title":"J Affect Disord"},{"issue":"4","key":"2020071612021034300_B3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/01.jcp.0000168879.03169.ce","article-title":"Sex differences in antidepressant response in recent antidepressant clinical trials","volume":"25","author":"Khan","year":"2005","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"2020071612021034300_B4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0165-1781(86)90063-6","article-title":"Forms of atypical depression and their response to antidepressant drugs","volume":"17","author":"Davidson","year":"1986","journal-title":"Psychiatry Res"},{"issue":"9","key":"2020071612021034300_B5","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1176\/appi.ajp.157.9.1445","article-title":"Gender differences in treatment response to sertraline versus imipramine in chronic depression","volume":"157","author":"Kornstein","year":"2000","journal-title":"Am J Psychiatry"},{"issue":"3","key":"2020071612021034300_B6","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0924-977X(01)00089-X","article-title":"Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile","volume":"11","author":"Martenyi","year":"2001","journal-title":"Eur Neuropsychopharmacol"},{"issue":"1\u20133","key":"2020071612021034300_B7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jad.2006.04.029","article-title":"Different gender response to serotonergic and noradrenergic antidepressants. 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