Aldosterone effects on salt appetite in adrenalectomized rats.
In order to establish the in vivo specificity of the mineralocorticoid recognition system of the rat brain, we investigated the potencies of aldosterone (ALDO) and corticosterone (CORT) in suppressing salt intake in adrenalectomized (ADX) rats. Increasing doses of ALDO (25, 50 and 100 ng/h), administered by Alzet minipump, suppress salt intake in a two-bottle preference test. CORT in doses up to 50 micrograms/h failed to mimic this effect of ALDO or to block it. Using the 50 micrograms/h dose of CORT, we demonstrated that the forebrain uptake of 3H-ALDO in vivo is suppressed by 60-75% when measured by isolation of cell nuclei or by quantitative autoradiography. The suppression is especially marked in the hippocampal formation, amygdala and septum, sites which also accumulate high levels of 3H-CORT. The uptake of 3H-ALDO by ADX rat forebrain can be suppressed approximately 95% by infusion of a specific antimineralocorticoid, RU 28318, at a dose of 50 micrograms/h. This dose also blocks ALDO action on salt intake. Lower doses of RU 28318 fail to block ALDO action or brain 3H-ALDO uptake. We conclude that: (1) ALDO is at least 500-fold more potent in vivo than CORT as a mineralocorticoid. (2) High uptake of 3H-ALDO in vivo by hippocampal formation, amygdala and septum in ADX rats is due in large part to binding to sites preferentially suppressed by CORT. The 3H-ALDO uptake (ca. 30%) after suppression by stress levels of CORT shows a regional distribution in which uptake is slightly higher in circumventricular structures than in hippocampal formation, septum or amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)
McEwen
B S
BS
Lambdin
L T
LT
Rainbow
T C
TC
De Nicola
A F
AF
D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; C041006:RU 28318; D003345:Corticosterone