Adrenalectomy augments in vivo release of norepinephrine in the paraventricular nucleus during immobilization stress.
Adrenalectomy (ADX) activates CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus and increases hypothalamic norepinephrine (NE) turnover in vitro. Immobilization (IMMO) markedly increases the release of NE into extracellular fluid in the PVN. The present study assessed whether ADX affects the release of NE in the PVN in vivo in conscious rats at baseline and during IMMO and whether cortisol (CORT) treatment attenuates the effects of ADX. Concentrations of NE, the NE metabolites dihydroxyphenylglycol and methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid were measured in microdialysate samples beginning 24 h after implantation of a microdialysis probe in the PVN. Seven to 10 days after ADX or ADX plus CORT (20 mg/kg.day via osmotic minipump), animals underwent IMMO for 2 h. Adrenalectomized rats had slightly higher baseline microdialysate NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and much larger IMMO-induced responses of these compounds than did sham-operated rats. CORT treatment abolished the ADX-induced augmentation of these responses. The results indicate that ADX, by removing endogenous glucocorticoids, augments IMMO-induced release and turnover of NE and amplifies the responses of catecholamine synthesis. Glucocorticoids, therefore, appear to exert feedback inhibition on stress-induced increments in the release of NE and catecholamine biosynthesis in the PVN.
Clinical Neuroscience Branch, National Institute of Mental Health and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
K
K
Pacák
R
R
Kvetnanský
M
M
Palkovits
K
K
Fukuhara
G
G
Yadid
I J
IJ
Kopin
D S
DS
Goldstein
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*
D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D000324:Adrenocorticotropic Hormone; C010117:3,4-dihydroxyphenylglycol; D003345:Corticosterone; D006854:Hydrocortisone; D009638:Norepinephrine