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.
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