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Life-Long Serotonin Reuptake Deficiency Results in Complex Alterations in Adrenomedullary Responses to Stress

Authors

  • OLGA A. TJURMINA,

    Corresponding author
    1. Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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    • *

      These authors contributed equally to the study.

  • INES ARMANDO,

    1. Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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    • *

      These authors contributed equally to the study.

  • JUAN M. SAAVEDRA,

    1. Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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  • QIAN LI,

    1. Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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  • DENNIS L. MURPHY

    1. Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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Address for correspondence: Olga A. Tjurmina, Laboratory of Clinical Science, NIMH, NIH, Bldg 10, Rm 3D41, 10 Center Dr., Bethesda, MD 20892, USA. Voice: 301-594-0218; fax: 301-402-0188. e-mail: ot3d@nih.gov

Abstract

Abstract: This study examined whether serotonin transporter (SERT) deficiency influences adrenal serotonin (5-HT), catecholamine and Angiotensin II (Ang II) systems, and the hormonal response to acute restraint stress. Control SERT mice (+/+) expressed high numbers of SERT binding sites in adrenal medulla. Fifteen minutes of restraint stress increased adrenal 5-HT, adrenomedullary tyrosine hydroxylase (TH) mRNA expression and plasma epinephrine (EPI), and norepinephrine levels without alterations in adrenal catecholamine content. In SERT+/+, these responses coincided with a significant increase in adrenomedullary Ang II AT2 receptor expression. SERT-deficient mice did not express SERT binding sites; their adrenal 5-HT was significantly depleted and further reduced after stress. They had exaggerated stress-induced EPI release into plasma, the increase in TH transcription did not occur, adrenal catecholamine content was decreased compared with SERT+/+, and stress induced a reduction rather than increase in the number of adrenomedullary AT2 receptors. SERT−/− mice also possessed decreased pituitary 5-HT. Their pituitary ACTH was reduced after stress, but stress-induced increases in plasma ACTH and corticosterone were not different from those of SERT+/+ mice. Our results indicate that SERT function not only restrains stress-induced EPI release but also is required for the increase in adrenal catecholamine synthesis and AT2 receptor expression.

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