Abstract
Animals with a history of sodium depletions exhibit increases in salt intake, a phenomenon described as the sensitization of sodium appetite. Using a novel experimental design, the present experiments investigated whether putative molecular markers of neural plasticity and changes in the message for components of the brain renin-angiotensin-aldosterone-system (RAAS) accompany the sensitization of sodium appetite. An initial set of experiments examined whether the glutamatergic N-methyl-d-aspartate receptor antagonist MK-801 would attenuate sodium appetite sensitization and prevent changes in mRNA expression associated with sensitization. Rats with repeated sodium depletions exhibited enhanced sodium appetite and mRNA expression for components of the RAAS in areas along the lamina terminalis (LT), a region of the brain that is important for the regulation of body fluid homeostasis, and these effects were significantly attenuated by MK-801 pretreatment. A second set of experiments investigated whether successive sodium depletions would elevate sodium intake and induce a pattern of fos-B staining consistent with the Δfos-B isoform in areas along the LT. The pattern of fos-B staining in the subfornical organ was consistent with the characteristics of Δfos-B expression. Specifically, fos-B/Δfos-B expression was increased 4 days after the last of a series of sodium depletions, fos-B/Δfos-B expression was nearly absent in control rats, and the quantity of fos-B/Δfos-B staining was directly associated with a history of sodium depletions. These findings demonstrate that the sensitization of sodium appetite is associated with sustained molecular alterations in the LT that are indicative of neural plasticity and upregulation of the central RAAS.