Sodium depletion activates the aldosterone-sensitive neurons in the NTS independently of thirst

Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1338-48. doi: 10.1152/ajpregu.00391.2006. Epub 2006 Oct 26.


Thirst and sodium appetite are both critical for restoring blood volume. Because these two behavioral drives can arise under similar physiological conditions, some of the brain sensory sites that stimulate thirst may also drive sodium appetite. However, the physiological and temporal dynamics of these two appetites exhibit clear differences, suggesting that they involve separate brain circuits. Unlike thirst-associated sensory neurons in the hypothalamus, the 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2) neurons in the rat nucleus tractus solitarius (NTS) are activated in close association with sodium appetite (16). Here, we tested whether the HSD2 neurons are also activated in response to either of the two physiological stimuli for thirst: hyperosmolarity and hypovolemia. Hyperosmolarity, produced by intraperitoneal injection of hypertonic saline, stimulated a large increase in water intake and a substantial increase in immunoreactivity for the neuronal activity marker c-Fos within the medial NTS, but not in the HSD2 neurons. Hypovolemia, produced by subcutaneous injection of hyperoncotic polyethylene glycol (PEG), stimulated an increase in water intake within 1-4 h without elevating c-Fos expression in the HSD2 neurons. The HSD2 neurons were, however, activated by prolonged hypovolemia, which also stimulated sodium appetite. Twelve hours after PEG was injected in rats that had been sodium deprived for 4 days, the HSD2 neurons showed a consistent increase in c-Fos immunoreactivity. In summary, the HSD2 neurons are activated specifically in association with sodium appetite and appear not to function in thirst.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
  • Aldosterone / pharmacology*
  • Animals
  • Biomarkers
  • Drinking
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Saline Solution, Hypertonic / administration & dosage
  • Saline Solution, Hypertonic / metabolism
  • Sodium, Dietary / metabolism*
  • Solitary Nucleus / cytology*
  • Thirst*
  • Time Factors


  • Biomarkers
  • Proto-Oncogene Proteins c-fos
  • Saline Solution, Hypertonic
  • Sodium, Dietary
  • Polyethylene Glycols
  • Aldosterone
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2