This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tjurmina, O. A. Articles by Murphy, D. L. Search for Related Content PubMed PubMed Citation Articles by Tjurmina, O. A. Articles by Murphy, D. L.

Exaggerated Adrenomedullary Response to Immobilization in Mice with Targeted Disruption of the Serotonin Transporter Gene

Laboratory of Clinical Science (O.A.T., D.L.M.) and Section on Pharmacology (I.A., J.M.S.), National Institute of Mental Health, and Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke (D.S.G.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Olga A. Tjurmina, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Building 10, Room 3D41, 10 Center Drive, MSC-1264, Bethesda, Maryland 20892-1264. E-mail: ot3d{at}nih.gov.

This study examined whether serotonin transporter (5-HTT) gene knockout influences adrenomedullary, sympathoneural, or hypothalamo-pituitary-adrenal responses to acute immobilization. In conscious, cannulated mice, arterial plasma concentrations of catecholamines, ACTH, and corticosterone were measured at baseline and after 15 min of immobilization. Tissue levels of serotonin (5-HT), catecholamines, and hormones were also measured in pituitary and adrenal glands. At baseline, adrenal and pituitary 5-HT concentrations in knockout (5-HTT^-/-) mice were markedly lower than those in littermate control (5-HTT^+/+) mice, whereas the groups did not differ in levels of catecholamines or hormones in plasma or tissue. Immobilization increased plasma levels of catecholamines, ACTH, and corticosterone in all genotypes. 5-HTT^-/- mice had exaggerated responses of plasma epinephrine to immobilization and significant reductions in adrenal epinephrine, norepinephrine, and 5-HT contents compared with values in littermate controls. Pituitary ACTH was significantly reduced after immobilization in 5-HTT^-/- mice only, but increases in plasma ACTH and corticosterone levels did not differ between genotypes. The results suggest that one 5-HTT function is to restrain adrenomedullary activation in response to immobilization. Exaggerated adrenomedullary responses seem to be an autonomic correlate of the anxiety-like behaviors in 5-HTT knockout mice.

This article has been cited by other articles:

				N. M. Sanders, C. W. Wilkinson, G. J. Taborsky Jr., S. Al-Noori, W. Daumen, A. Zavosh, and D. P. Figlewicz The selective serotonin reuptake inhibitor sertraline enhances counterregulatory responses to hypoglycemia Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E853 - E860. [Abstract] [Full Text] [PDF]

				A. Li and E. Nattie Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia J. Physiol., May 1, 2008; 586(9): 2321 - 2329. [Abstract] [Full Text] [PDF]

				C. Otte, J. McCaffery, S. Ali, and M. A. Whooley Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study Am J Psychiatry, September 1, 2007; 164(9): 1379 - 1384. [Abstract] [Full Text] [PDF]

				A. M. Curtis, Y. Cheng, S. Kapoor, D. Reilly, T. S. Price, and G. A. FitzGerald Circadian variation of blood pressure and the vascular response to asynchronous stress PNAS, February 27, 2007; 104(9): 3450 - 3455. [Abstract] [Full Text] [PDF]

				C. L. Wellman, A. Izquierdo, J. E. Garrett, K. P. Martin, J. Carroll, R. Millstein, K.-P. Lesch, D. L. Murphy, and A. Holmes Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice J. Neurosci., January 17, 2007; 27(3): 684 - 691. [Abstract] [Full Text] [PDF]

				S. J. Warden, A. G. Robling, M. S. Sanders, M. M. Bliziotes, and C. H. Turner Inhibition of the Serotonin (5-Hydroxytryptamine) Transporter Reduces Bone Accrual during Growth Endocrinology, February 1, 2005; 146(2): 685 - 693. [Abstract] [Full Text] [PDF]

				C. S. Barr, T. K. Newman, M. Schwandt, C. Shannon, R. L. Dvoskin, S. G. Lindell, J. Taubman, B. Thompson, M. Champoux, K. P. Lesch, et al. Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques PNAS, August 17, 2004; 101(33): 12358 - 12363. [Abstract] [Full Text] [PDF]

				D. L. Murphy, A. Lerner, G. Rudnick, and K.-P. Lesch Serotonin Transporter: Gene, Genetic Disorders, and Pharmacogenetics Mol. Interv., April 1, 2004; 4(2): 109 - 123. [Abstract] [Full Text] [PDF]

				C. Bregonzio, I. Armando, H. Ando, M. Jezova, G. Baiardi, and J. M. Saavedra Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G414 - G423. [Abstract] [Full Text] [PDF]