INTRACEREBRAL ADMINISTRATION OF MINERALOCORTICOID RECEPTOR ANTISENSE OLIGONUCLEOTIDES ATTENUATE ADRENAL STEROID-INDUCED SALT APPETITE IN RATS

The amygdala contains mineralocorticoid (MR) and glucocorticoid recept ors (GR) involved in the arousal of salt appetite. In the present inve stigation, MR antisense oligonucleotides injected into the amygdala in hibited salt appetite induced by systemic desoxycorticosterone (DOCA) but not adrenalectomy (ADX). In contrast, GR antisense or scrambled ol igonucleotides had no effect on stimulated salt intake. MR antisense o ligomers also decreased MR but not GR in amygdala, whereas GR antisens e oligomers decreased GR but not MR. Immunocytochemical labelling of t he biotinylated MR antisense revealed that distribution of the oligome r was restricted to the injection site, with incorporation in neurons and neighboring glial cells. Together, these data demonstrate the util ity of receptor antisense oligonucleotides for investigating the centr al actions of adrenal steroids and the role of amygdala MR in DOCA-ind uced sodium intake.