A Novel Class of Orally-Applied Inhibitors of Aggressive Behavior

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DESCRIPTION (provided by applicant): Peptide YY3-36 (PYY3-36) is an important hormone that is released post-prandially into the bloodstream from gut epithelial cells. Its secretion is related to caloric intake, and it induces satiety by acting on Y2 receptors in the brain. Recent research conducted in the PI's laboratory indicates that PYY3-36 is also secreted by the salivary glands where it plays a significant role in regulation of feeding. Accordingly, our research originally focused on the impact of salivary PYY3-36 on food intake. However, we serendipitously discovered that injection of a recombinant viral vector containing preproPYY into the submandibular salivary gland (increasing long-term salivary PYY expression) eliminated spontaneous aggression in mice, probably through signaling to limbic and hypothalamic regions of the brain. The objective of this proposal is to extend that initial finding to a rat model of experimentally-induced aggression so that we may systematically explore potential pharmacological and genetic approaches for treatment of aggressive behavior disorders in human patients. The study will characterize the heretofore unidentified functions of salivary PYY3-36 in regulation of aggressive behavior. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to show that experimentally-induced elevated levels of the gastric Peptide YY in saliva of male rat reduce their spontaneous aggression. The study will characterize the heretofore unidentified functions of salivary PYY3-36 in regulation of aggressive behavior. Successful completion of these studies could lead to a novel therapeutic application for the treatment of acute violent outbursts in psychotic patients.