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).
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
{"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).","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","doi":"10.1080/10253890.2025.2457765","DOIUrl":null,"url":null,"abstract":"<p><p>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 (E<sub>2</sub>), 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 E<sub>2</sub>-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 E<sub>2</sub>. 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 E<sub>2</sub> + 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.</p>","PeriodicalId":51173,"journal":{"name":"Stress-The International Journal on the Biology of Stress","volume":"28 1","pages":"2457765"},"PeriodicalIF":2.6000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801257/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stress-The International Journal on the Biology of Stress","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1080/10253890.2025.2457765","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The journal Stress aims to provide scientists involved in stress research with the possibility of reading a more integrated view of the field. Peer reviewed papers, invited reviews and short communications will deal with interdisciplinary aspects of stress in terms of: the mechanisms of stressful stimulation, including within and between individuals; the physiological and behavioural responses to stress, and their regulation, in both the short and long term; adaptive mechanisms, coping strategies and the pathological consequences of stress.
Stress will publish the latest developments in physiology, neurobiology, molecular biology, genetics research, immunology, and behavioural studies as they impact on the understanding of stress and its adverse consequences and their amelioration.
Specific approaches may include transgenic/knockout animals, developmental/programming studies, electrophysiology, histochemistry, neurochemistry, neuropharmacology, neuroanatomy, neuroimaging, endocrinology, autonomic physiology, immunology, chronic pain, ethological and other behavioural studies and clinical measures.