Endocrinology, Vol 136, 4814-4819, Copyright © 1995 by Endocrine Society

ARTICLES

Catecholaminergic inhibition by hypercortisolemia in the paraventricular nucleus of conscious rats

K Pacak, M Palkovits, R Kvetnansky, P Matern, C Hart, IJ Kopin and DS Goldstein
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.

Administration of glucocorticoids decreases the release of corticotropin-releasing hormone and in vitro turnover of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO) markedly increases NE release and stimulates corticotropin-releasing hormone neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo indexes of catecholaminergic activation in the PVN. Microdialysis was used to simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined based on elevations of 3,4- dihydroxyphenylalanine levels after local perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25 mg/kg.day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and significantly smaller levels of all these compounds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4- dihydroxyphenylalanine at baseline and during IMMO than VEH-treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses were reduced in CORT-treated rats. The results indicate that chronic hypercortisolemia decreases basal levels and stress-induced increments in indexes of release, metabolism, turnover, and synthesis of catecholamines in the PVN and suggest that glucocorticoids restrain the limit of hypothalamo-pituitary-adrenocortical axis activation during stress by attenuating catecholamine synthesis and release in the PVN.

This article has been cited by other articles:

				D. A. Sandoval, L. Ping, R. A. Neill, B. Gong, K. Walsh, and S. N. Davis Brain region-dependent effects of dexamethasone on counterregulatory responses to hypoglycemia in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R413 - R419. [Abstract] [Full Text] [PDF]

				D. A. Sandoval, L. Ping, R. A. Neill, S. Morrey, and S. N. Davis The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats Diabetes, March 1, 2004; 53(3): 679 - 686. [Abstract] [Full Text] [PDF]

				Z.'e. Hochberg, K. Pacak, and G. P. Chrousos Endocrine Withdrawal Syndromes Endocr. Rev., August 1, 2003; 24(4): 523 - 538. [Abstract] [Full Text] [PDF]

				N. M. Sanders and S. Ritter Acute 2DG-Induced Glucoprivation or Dexamethasone Abolishes 2DG-Induced Glucoregulatory Responses to Subsequent Glucoprivation Diabetes, December 1, 2001; 50(12): 2831 - 2836. [Abstract] [Full Text] [PDF]

				K.-H. Jeong, L. Jacobson, K. Pacak, E. P. Widmaier, D. S. Goldstein, and J. A. Majzoub Impaired Basal and Restraint-Induced Epinephrine Secretion in Corticotropin-Releasing Hormone- Deficient Mice Endocrinology, March 1, 2000; 141(3): 1142 - 1150. [Abstract] [Full Text] [PDF]

				S. C. Weninger, L. L. Peters, and J. A. Majzoub Urocortin Expression in the Edinger-Westphal Nucleus Is Up-Regulated by Stress and Corticotropin-Releasing Hormone Deficiency Endocrinology, January 1, 2000; 141(1): 256 - 263. [Abstract] [Full Text] [PDF]