Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)

Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses....

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Main Authors: Jamie L. Scholl, Joshua T. Rogers, Na Feng, Gina L. Forster, Michael J. Watt, Jazmine D. W. Yaeger, Michael W. Buchanan, Christopher A. Lowry, Kenneth J. Renner
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Stress
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Online Access:https://www.tandfonline.com/doi/10.1080/10253890.2025.2457765
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author Jamie L. Scholl
Joshua T. Rogers
Na Feng
Gina L. Forster
Michael J. Watt
Jazmine D. W. Yaeger
Michael W. Buchanan
Christopher A. Lowry
Kenneth J. Renner
author_facet Jamie L. Scholl
Joshua T. Rogers
Na Feng
Gina L. Forster
Michael J. Watt
Jazmine D. W. Yaeger
Michael W. Buchanan
Christopher A. Lowry
Kenneth J. Renner
author_sort Jamie L. Scholl
collection DOAJ
description Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E2), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E2-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E2. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E2 + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.
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spelling doaj-art-bed0b453b3a24c008fc7a1238de7e95e2025-02-03T13:01:02ZengTaylor & Francis GroupStress1025-38901607-88882025-12-0128110.1080/10253890.2025.2457765Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)Jamie L. Scholl0Joshua T. Rogers1Na Feng2Gina L. Forster3Michael J. Watt4Jazmine D. W. Yaeger5Michael W. Buchanan6Christopher A. Lowry7Kenneth J. Renner8Basic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USADepartment of Biology and Center for Brain and Behavior Research, University of South Dakota, SD, USADepartment of Biology and Center for Brain and Behavior Research, University of South Dakota, SD, USABasic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USABasic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USADepartment of Biology and Center for Brain and Behavior Research, University of South Dakota, SD, USADepartment of Biology and Center for Brain and Behavior Research, University of South Dakota, SD, USADepartment of Integrative Physiology, Department of Psychology and Neuroscience, Center for Neuroscience, and Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO, USABasic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USAPrevious studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E2), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E2-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E2. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E2 + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.https://www.tandfonline.com/doi/10.1080/10253890.2025.2457765Extraneuronal monoamine transporterhypothalamuslordosisOCT3steroidsuptake2
spellingShingle Jamie L. Scholl
Joshua T. Rogers
Na Feng
Gina L. Forster
Michael J. Watt
Jazmine D. W. Yaeger
Michael W. Buchanan
Christopher A. Lowry
Kenneth J. Renner
Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
Stress
Extraneuronal monoamine transporter
hypothalamus
lordosis
OCT3
steroids
uptake2
title Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
title_full Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
title_fullStr Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
title_full_unstemmed Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
title_short Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3)
title_sort corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen and progesterone dependent manner in adult female rats potential role of organic cation transporter 3 oct3
topic Extraneuronal monoamine transporter
hypothalamus
lordosis
OCT3
steroids
uptake2
url https://www.tandfonline.com/doi/10.1080/10253890.2025.2457765
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