The amygdala: site of genomic and nongenomic arousal of aldosterone-induced sodium intake.
BACKGROUND.: Mineralocorticoids act on the brain to influence sodium intake, and they do so via intracellular type I receptors and possibly also via a direct membrane action, as they do in the kidney. One brain area implicated by lesion studies investigating the regulation of sodium appetite aroused by adrenal steroids is the amygdala.


METHODS
To examine the mechanism by which mineralocorticoids act in the amygdala to arouse salt intake via a genomic and or membrane mode of action, rats were bilaterally fitted with cannulae directed to terminate in the amygdala. The genomic action of mineralocorticoids in arousing sodium intake was investigated by the administration of antisense oligodeoxynucleotides (ASDNs) against the mineralocorticoid receptor, and its effects on deoxycorticosterone (DOCA)-induced sodium intake over the course of several days was examined. The nongenomic action of mineralocorticoids on sodium intake was investigated by implantation into the amygdala of DOCA, aldosterone (ALDO), or their A-ring-reduced tetrahydro derivatives, 15 minutes prior to access to saline. Sodium intake was monitored immediately thereafter.


RESULTS
Treatment of rats in the amygdala with ASDN against the mineralocorticoid receptor inhibited DOCA-induced sodium intake, whereas ASDN against the glucocorticoid receptor or sense/scrambled sequences had no effect. DOCA and ALDO increased saline intake within 15 minutes after steroid application. Similarly, the application of A-ring-reduced 3beta,5beta tetrahydroaldosterone and 5 alpha-tetrahydrodeoxycorticosterone produced the same increases in sodium intake.


CONCLUSIONS
Together, the data imply that adrenal steroids, in addition to acting through classic cytosolic receptors, may also act on membrane receptor systems, producing rapid changes in behavior.
Sakai
R R
RR
Department of Animal Biology, University of Pennsylvania, Philadelphia, PA, USA. randall.sakai@psychiatry.uc.edu
McEwen
B S
BS
Fluharty
S J
SJ
Ma
L Y
LY
D000450:Aldosterone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001143:Arousal / Q000502:physiology*; D003345:Corticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D016678:Genome; D006727:Hormone Antagonists / Q000494:pharmacology; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012964:Sodium; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D016376:Oligonucleotides, Antisense; D018079:Receptors, GABA; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D003900:Desoxycorticosterone; D000450:Aldosterone; C041006:RU 28318; D012964:Sodium; D003345:Corticosterone