A Novel Class of Orally-Applied Inhibitors of Aggressive Behavior

描述（由申请人提供）：肽YY 3 -36（PYY 3 -36）是一种重要的激素，餐后从肠上皮细胞释放到血流中。它的分泌与热量摄入有关，它通过作用于大脑中的Y2受体来诱导饱腹感。最近在PI实验室进行的研究表明，PYY 3 -36也由唾液腺分泌，在调节摄食方面起着重要作用。因此，我们的研究最初集中在唾液PYY 3 -36对食物摄入的影响上。然而，我们偶然发现，将含有preproPYY的重组病毒载体注射到下颌下唾液腺中（增加长期唾液PYY表达）消除了小鼠的自发攻击性，这可能是通过向大脑边缘系统和下丘脑区域发出信号。本提案的目的是将最初的发现扩展到实验诱导的攻击性大鼠模型，以便我们可以系统地探索治疗人类患者攻击性行为障碍的潜在药理学和遗传学方法。该研究将表征唾液PYY 3 -36在调节攻击行为中迄今未鉴定的功能。 公共卫生相关性：本提案的目的是表明实验诱导的雄性大鼠唾液中胃肽YY水平升高可降低其自发攻击性。该研究将表征唾液PYY 3 -36在调节攻击行为中迄今未鉴定的功能。这些研究的成功完成可能会导致一种新的治疗应用，用于治疗精神病患者的急性暴力爆发。

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.