This application is the resubmission of the competing renewal of our Program Project Grant (MH43787) entitled """"""""The Neurohormonal Mechanisms of Ingestive Behavior."""""""" The major goal of this research program is to employ experimental tools in cell and molecular biology, pharmacology, biochemistry, neurophysiology, and neuroanatomy, in the analysis of motivated behavior. The motivational system under investigation is salt appetite in the rat. It is now well established that a complex system of interacting excitatory and inhibitory stimuli is involved in the central control of this ingestive behavior. The peptide and steroid hormones that mediate these opposing signals in the brain have been identified and they can be readily studied. Thus, salt appetite is a paradigmatic system for the study of the neuroendocrinology of motivated behavior. The Program Project Grant is divided into four main projects. In one Project 1, c-fos immunocytochemistry is used to identify the brain areas involved in excitation and inhibition of salt appetite. The phenotypic identity of activated cells is then established, as is their neural circuitry. In Project 2, genomic and non-genomic actions of steroids on the neural substrates of salt appetite are investigated. Genomic effects under investigation include regulation of neuropeptide systems such as angiotensin and oxytocin, whereas non-genomic effects are studied as manifestations of steroid interactions with GABA receptors. In another Project, behavioral and electrophysiological techniques are combined to study the integration of gustatory and motivational signals, and hormonal modulation of neural activity throughout the central projects of the taste system is examined. Finally, in another Project, cell and molecular techniques are used to delineate the functional properties of angiotensin and oxytocin receptors in brain. In addition, adrenal steroid regulation of peptide receptor expression is examined, as is the behavioral effects of antisense blockade of these receptors. These four projects collectively form a program of study that is multidisciplinary in nature and ideally suited to investigation of fundamental issues common to the brain's control of behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program Projects (P01)
Project #
5P01MH043787-07
Application #
2519721
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1989-02-01
Project End
2001-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pharmacology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lucas, Louis R; Grillo, Claudia A; McEwen, Bruce S (2007) Salt appetite in sodium-depleted or sodium-replete conditions: possible role of opioid receptors. Neuroendocrinology 85:139-47
Sakai, Randall R (2004) The future of research on thirst and salt appetite. Appetite 42:15-9
Daniels, Derek; Fluharty, Steven J (2004) Salt appetite: a neurohormonal viewpoint. Physiol Behav 81:319-37
Lundy Jr, Robert F; Caloiero, Vince; Bradley, Courtney et al. (2004) Furosemide-induced food avoidance: evidence for a conditioned response. Physiol Behav 81:397-408
Lucas, Louis R; Grillo, Claudia A; McEwen, Bruce S (2003) Involvement of mesolimbic structures in short-term sodium depletion: in situ hybridization and ligand-binding analyses. Neuroendocrinology 77:406-15
Fitts, Douglas A; Thornton, Simon N; Ruhf, Alexandra A et al. (2003) Effects of central oxytocin receptor blockade on water and saline intake, mean arterial pressure, and c-Fos expression in rats. Am J Physiol Regul Integr Comp Physiol 285:R1331-9
Hines, John; Fluharty, Steven J; Yee, Daniel K (2003) Structural determinants for the activation mechanism of the angiotensin II type 1 receptor differ for phosphoinositide hydrolysis and mitogen-activated protein kinase pathways. Biochem Pharmacol 66:251-62
Tamura, R; Norgren, R (2003) Intracranial renin alters gustatory neural responses in the nucleus of the solitary tract of rats. Am J Physiol Regul Integr Comp Physiol 284:R1108-18
Lucas, Louis R; Reagan, Lawrence P; Akama, Keith T et al. (2003) Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat. Brain Res 960:252-8
Bello, Nicholas T; Lucas, Louis R; Hajnal, Andras (2002) Repeated sucrose access influences dopamine D2 receptor density in the striatum. Neuroreport 13:1575-8

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