MINERALOCORTICOID RECEPTOR IN THE NUCLEUS OF THE SOLITARY TRACT STIMULATES SALINE INTAKE DURING 4TH VENTRICULAR INFUSIONS OF ALDOSTERONE Running Title: NTS and saline intake

The purpose of this study was to determine if neurons within the NTS that express the mineralocorticoid receptor (MR) play a role in aldosterone stimulation of salt intake. Adult WKY rats received microinjections into the NTS of a short-hairpin RNA for the MR, to sitespecifically reduce levels of the MR by RNA interference (shRNA; n=9), or scrambled RNA as a control (scRNA; n=8). After injection of the viral construct, aldosterone-filled osmotic minipumps were implanted subcutaneously and connected to a cannula extending into the 4th ventricle to infuse aldosterone at a rate of 25ng/h. Prior to and after surgeries, rats had ad libitum access to normal sodium (0.26%) rat chow and two graduated drinking bottles filled with either distilled water or 0.3M NaCl. Prior to surgeries, basal saline intake was 1.6ml ± 0.6ml in the scRNA group and 1.56ml ± 0.6ml in the shRNA group. 24 days post-surgery, saline intake was elevated to a greater extent in the scRNA group (5.9ml± 1.07ml) than in the shRNA group (2.41ml ± 0.6ml). Post-mortem immunohistochemistry revealed a significant reduction in the number of NTS neurons exhibiting immunoreactivity for MR in shRNA-injected rats (23 ± 1 cells/section) vs. scRNA-injected rats (33 ± 2 cells/section; p=.008). shRNA did not alter the level of HSD2 protein in the NTS as judged by the number of HSD2 immunoreactive neurons. These results suggest that 4th ventricular infusions of aldosterone stimulate saline intake and that this stimulation is at least in part mediated by hindbrain NTS neurons that express MR.