Title

Life-long serotonin reuptake deficiency results in complex alterations in adrenomedullary responses to stress

Document Type

Conference Proceeding

Publication Date

1-1-2004

Journal

Annals of the New York Academy of Sciences

Volume

1018

DOI

10.1196/annals.1296.011

Keywords

Angiotensin II receptors; Epinephrine; Serotonin; SERT deficiency; Stress; TH mRNA

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 AT 2 receptor expression.

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