Intracerebral Administration of Mineralocorticoid Receptor Antisense Oligonucleotides Attenuate Adrenal Steroid-Induced Salt Appetite in Rats

Abstract

The amygdala contains mineralocorticoid (MR) and glucocorticoid receptors (GR) involved in the arousal of salt appetite. In the present investigation, MR antisense oligonucleotides injected into the amygdala inhibited salt appetite induced by systemic desoxycorticosterone (DOCA) but not adrenalectomy (ADX). In contrast, GR antisense or scrambled oligonucleotides had no effect on stimulated salt intake. MR antisense oligomers also decreased MR but not GR in amygdala, whereas GR antisense oligomers decreased GR but not MR. Immunocytochemical labelling of the biotinylated MR antisense revealed that distribution of the oligomer was restricted to the injection site, with incorporation in neurons and neighboring glial cells. Together, these data demonstrate the utility of receptor antisense oligonucleotides for investigating the central actions of adrenal steroids and the role of amygdala in MR in DOCA-induced sodium intake.