OPIOID RECEPTOR SUBTYPE ROLES IN RAT FEEDING BEHAVIOR

本提案打算调查阿片类药物的性质。 受体亚型参与已建立的喂养模型 肥胖、监管变化和压力。在抑制的同时 继阿片受体拮抗剂纳洛酮之后，纳洛酮已经 作为食物摄入中含有内源性阿片类药物的证据， 它不能具体说明阿片受体亚型参与，因为它 短作用时间及其与多种阿片类药物的相互作用 受体亚型。纳洛酮是一种有效且持久的 阿片受体拮抗剂选择性结合MU1结合部位 代表两种阿片类药物的共同高亲和力结合部位 和脑啡肽。最近的研究表明，Halox-one和 纳洛酮在某些喂养模式中产生不同的效果 以及在其他地方的类似影响，从而表明MU1位点在 一些，但不是所有形式的进食行为。进一步鸦片类药物 受体亚型参与的研究可以从使用 β-纤溶酶原激活剂，使u受体烷化，ici 174864，一种 受体拮抗剂MR2266，可能是kappa受体拮抗剂 以及β-CNA，它能使所有阿片受体烷化。第一 明确目标将分析这些抗激动剂的有效性。 根据剥夺诱导的摄食在一定剂量范围内 和中心注射。第二个具体目标将调查 MU1和其他位点在长期体重增加模型中的作用 通过长期给予上述拮抗剂和食物摄入量 为了遗传追逐大鼠，大鼠下丘脑内侧侧部用刀割伤 以及下丘脑室旁损伤的大鼠。第三 特定目标将调查MU1和其他站点在 通过尖锐地应用上述方法建立食物摄入量的短期模型 胰岛素治疗大鼠、夹尾巴大鼠的拮抗剂 压力，老鼠提供美味的食物和液体。

The present proposal intends to investigate the nature of opioid receptor subtype involvement in established feeding models related to obesity, regulatory changes and stress. While suppression of feeding following the opiate receptor antagonist, naloxone has been used as evidence implicating the endogenous opioids in food intake, it cannot specify opioid receptor subtype involvement given its short duration of action and its interaction with multiple opioid receptor subtypes. Naloxonazine is a potent and long-lasting opioid receptor antagonist selective for the mu1 binding site which represents a common, high-affinity binding site for both opiates and enkephalins. Recent work has demonstrated that halox-one and naloxonazine produce different effects in some feeding paradigms and similar effects in others, thereby implicating the mu1 site in some, but not all forms of feeding behavior. Further opiate receptor subtype involvement can be implied from studies using beta-FNA, which alkylates mu receptors, ICI 174864, a delta receptor antagonist, MR2266, a putative kappa receptor antagonist and beta-CNA, which alkylates all opiate receptors. The first specific aim will analyze the effectiveness of these anti-agonists upon deprivation-induced feeding across a dose range of systematic and central injections. The second specific aim will investigate the role of mu1 and other sites in long-term models of weight gain and food intake by chronically administering the above antagonists to genetically-chase rats, rats with medial hypothalamic knife cuts and rats with hypothalamic paraventricular lesions. The third specific aim will investigate the role of mu1 and other sites in short-term models of food intake by acutely administering the above antagonists to insulin-treated rats, rats receiving tail-pinch stress, and rats offered palatable foods and liquids.