CATECHOLAMINERGIC INHIBITION BY HYPERCORTISOLEMIA IN THE PARAVENTRICULAR NUCLEUS OF CONSCIOUS RATS

Administration of glucocorticoids decreases the release of corticotrop in-releasing hormone and in vitro turnover of norepinephrine (NE) in t he paraventricular nucleus (PVN) of the hypothalamus, and immobilizati on (IMMO) markedly increases NE release and stimulates corticotropin-r eleasing hormone neurons in the PVN. This study assessed whether hyper cortisolemia affects in vivo indexes of catecholaminergic activation i n the PVN. Microdialysis was used to simultaneously measure PVN microd ialysate concentrations of NE, the neuronal NE metabolite dihydroxyphe nylglycol, 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. Cortiso l (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, d ihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenyla cetic acid levels and significantly smaller levels of all these compou nds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4-dihydroxyphenylal anine at baseline and during IMMO than VEH-treated rats. Basal and IMM O-induced plasma ACTH and corticosterone responses were reduced in COR T-treated rats. The results indicate that chronic hypercortisolemia de creases basal levels and stress-induced increments in indexes of relea se, metabolism, turnover, and synthesis of catecholamines in the PVN a nd suggest that-glucocorticoids restrain the limit of hypothalamo-pitu itary-adrenocortical axis activation during stress by attenuating cate cholamine synthesis and release in the PVN.