1985 — 1991 |
Epstein, Alan N |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neurological Bases of Feeding and Drinking @ University of Pennsylvania
Small doses of systemic mineralocorticoid (DOCA or aldosterone) combined with infusions of low doses of angiotensin II into the cerebral ventricles of the sodium replete rat induce a rapid, reliable, and robust appetite for salt, and the salt appetite of the sodium deplete rat is suppressed by interference with the cerebral actions of angiotensin II with drugs that prevent its synthesis or block its receptors. These findings support the hypothesis that excess sodium intake is provoked by a synergy of action in the brain of the two hormones of renal sodium conservation - angiotensin II (Ang II) and aldosterone (ALDO). Endogenous Ang I, Ang II, and ALDO will be measured by radioimmune assay in the sodium deficient, the adrenalectomized, and the drug or hormone treated rat to evaluate the hypothesis directly. Blockade of synthesis of endogenous Ang II with orally self-administered captopril (Squibb) will test the idea that in the adrenalectomized rat, in which angiotensin must act without aldosterone, the appetite for salt is completely dependent on angiotensin. The role of endogenous ALDO will be evaluated in the intact rat by varying the salt content of its diet and by using a new mineralocorticoid receptor blocker (RU 28318) that is potent and specific. Renin-angiotensin systems exist both in the periphery and in the brain. Their potencies for arousal of salt appetite by synergy with ALDO will be compared by contrasting the results of intravenous infusion of Ang II or of competitive antagonists of Ang II with those already obtained with intracranial infusion of the same agents. In addition, the neurological mechanisms that may mediate the synergistic effect of the hormones will be studied with emphasis on the circumventricular organs, as will the effects of the synergy treatment and the excess salt intake that it produces on the rat's blood pressure. The ontogeny of the appetite will be studied in newborn rats, and its phylogeny will be studied in the pigeon. Excess salt intake is implicated in the etiology of hypertensive disease. An understanding of its hormonal causes could lead to rational chemical therapies and to reductions of salt intake in humans at risk for hypertension.
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1985 — 1986 |
Epstein, Alan N |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ontogeny of Ingestive Behavior @ University of Pennsylvania
The development of feeding and drinking behavior will be studied in the suckling rat with techniques that 1) allow for the measurement of both its milk and water intake, and 2) permit the injection of chemical agents into its brain in a benign procedure that does not interfere with its subsequent behavior. We will continue to study the ontogenetic calendar with which the developing brain becomes responsive to agents that arouse (renin, angiotensin, hypersomotic solutes) or suppress drinking (prostaglandin Es), and that arouse feeding (norepinephrine, 2-deoxy-D-glucose). Having found two treatments that induce hyperphagia in the newborn (1) complete subdiaphragmatic denervation, + (2) removal of a preweanling rat from the litter for free-feeding through an oral catheter, we will investigate the mechanism of both and their implications for control of suckling and adult feeding. We will study the effects of early nutritional history on adult drinking behavior. Weanling rats will be raised on dilute liquid diet or will be desalivated. Both regimes will prevent body water losses, but one (the former) will provide excess oral lubrication, and the other will dry the mouth. The temporal pattern of the animals' spontaneous meals and drafts and their responsiveness to deficit signals will be studied when normal oral conditions are restored and when the animals are challenged with deficits in adulthood.
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1985 — 1988 |
Epstein, Alan N |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Predoctoral Training in Behavioral Neuroscience @ University of Pennsylvania |
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1989 — 1991 |
Epstein, Alan N |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Neurohormonal Mechanisms of Ingestive Behavior @ University of Pennsylvania
This is an application for a NEUROSCIENCE WORK GROUP IN MENTAL HEALTH that will bring together eleven senior investigators for collaborative research on the neurohormonal mechanisms of salt appetite in the rat. Recent behavioral-endocrinological research has demonstrated that salt appetite is an hormonally induced behavior. It is aroused by the synergistic action in the brain of angiotensin and aldosterone which are also the hormones of renal sodium conservation. The Work Group will combine behavioral- endocrinological methods with state-of-the-art biological techniques (cytosol receptor analysis, membrane pharmacology, microiontophoresis and electrophysiology, and cellular biochemistry) in a broad-ranging reductionist analysis of the neural mechanisms by which angiotensin and aldosterone act to arouse a specific motivated behavior that depends for its expression on a single sensory channel (the salt taste). Six Projects are proposed. They are closely integrated around the central question: What is the cellular and molecular nature of the neural mechanism by which angiotensin and associated hormones (aldosterone and atrial natriuretic hormone) mobilize salt. appetite?
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1989 — 1990 |
Epstein, Alan N |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ontogeny of Salt Intake @ University of Pennsylvania |
1 |
1989 — 1991 |
Epstein, Alan N |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Pre and Postdoctoral Training in Behavioral Neuroscience @ University of Pennsylvania |
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