OPIOID RECEPTOR SUBTYPE ROLES IN RAT FEEDING BEHAVIOR

本提案旨在研究阿片类药物的性质， 受体亚型参与已建立的喂养模型相关 肥胖、调节变化和压力。 虽然压制 在阿片受体拮抗剂纳洛酮给药后， 作为食物摄入中内源性阿片类物质的证据， 它不能指定阿片受体亚型参与， 短作用时间及其与多种阿片类药物相互作用 受体亚型 纳洛嗪是一种强效且持久的 对μ 1结合位点具有选择性的阿片受体拮抗剂 代表了两种阿片类药物共同的高亲和力结合位点 和脑啡肽。 最近的研究表明， 纳洛嗪在不同的喂养模式下产生不同的作用 在其他方面也有类似的效果，从而暗示mu 1位点 一些，但不是所有形式的进食行为。 更多鸦片 受体亚型参与可以从使用 β-FNA，其烷基化μ受体，ICI 174864，δ 受体拮抗剂，MR 2266，一种推定的κ受体拮抗剂 和β-CNA，它会使所有阿片受体烷基化 第一 具体目标将分析这些抗激动剂的有效性 在整个剂量范围内的系统性剥夺诱导喂养后， 和中央注射。 第二个具体目标将调查 MU 1和其他位点在长期体重增加模型中的作用 和食物摄入 对老鼠进行基因追踪， 和下丘脑室旁损害的大鼠。 第三 specific aim将研究mu 1和其他位点在 通过急性给予上述物质的食物摄入的短期模型 胰岛素治疗大鼠的拮抗剂，接受夹尾的大鼠 压力，老鼠提供可口的食物和液体。

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.