The central nervous system controls sodium and water metabolism and the motivated behaviors of thirst and salt appetite after selective dehydrations in rats. The circumventricular organs (CVOs) of the forebrain, the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), may participate in the generation of thirst and salt appetite by detecting elevated levels of angiotensin (ANG) II and osmolality in the blood. Recent evidence also suggests that the brain oxytocinergic system chronically inhibits salt appetite, and the full expression of this behavior may rely as much on the removal of this inhibition as on the activation of excitatory systems such as ANG II. The proposed experiments will elucidate how the SFO and OVLT interact with the rest of the brain to provoke an integrated behavioral and physiological response to dehydration by participating in these excitatory and inhibitory events in the brain.
Aim 1 will determine if a combined lesion of the SFO and OVLT will be more effective than individual lesions in abolishing salt appetite during sodium depletion.
Aim 2 will evaluate the effects of CVO lesions and different kinds of dehydration on the density and distribution of ANG II type AT1 receptors in the other CVOs and relevant areas of the brain as measured by in vitro receptor autoradiography.
Aim 3 will investigate whether the dipsogenic responses induced by intracerebroventricular administration of oxytocin antagonists involves the forebrain CVOs.
Aim 4 will determine if prolonged stimulation of the forebrain CVOs by ANG II causes a change in function of the CVOs that may account for the unexplained delay in the emergence of salt appetite after sodium depletion.
Aim 5 will study the interdependence of the SFO and the rest of the preoptic area and hypothalamus during intravenous administration of ANG II or hypernatremia by examining the expression of Fos-like immunoreactivity in these brain regions after a disconnection of all afferent and efferent fibers of the SFO. These studies will help us to analyze how the CVOs work together with each other and with the rest of the brain to generate these behaviors. The results will have implications for the central control of blood pressure and endocrine secretions as well as behavior during various challenges to body hydration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022274-16
Application #
6667218
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Mitler, Merrill
Project Start
1985-09-23
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
16
Fiscal Year
2003
Total Cost
$273,126
Indirect Cost
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195