OPIOID SYSTEMS IN VENTRAL STRIATUM AND FOOD REWARD

鸦片类药物，如海洛因和吗啡，构成了主要类别之一 世界上滥用药物最多的国家。虽然阿片成瘾的治疗 仍然是有问题的，我们的将军已经取得了巨大的进步 对这些药物在大脑中作用的系统的了解。这个 内源性阿片类药物被认为在多种生物中发挥着重要作用。 疼痛调节、情感和情绪、对压力的反应、 和增援。研究的一个主要领域是阿片类药物。 调停喂食和饮酒。一种已经被接受的假设 相当大的支持率表示，阿片类药物具体规范 食物的有益的或享乐的方面。此外，临床研究结果表明 阿片类药物的功能障碍可能在某种程度上与人类的疾病有关 以过度的渴望、冲动的行为和失去 控制力，就像暴食症和酗酒。在过去的几年里，我们 实验室已经调查了阿片类药物操作对 伏隔核对摄食行为的影响。这种大脑结构，是 腹侧纹状体被认为是 阿片类药物和精神刺激性药物的强化作用。我们的研究是为了 数据显示，伏隔核内微量注射吗啡 导致进食行为和过量进食的显著增加 入口处。这种作用主要是通过Mu受体介导的。 在解剖学上定位于腹侧边缘传入的纹状体区域。 此外，条件喂养是在控制或假的情况下发展起来的。 对多次微量注射阿司匹林的动物进行注射 吗啡。向该区域注射阿片类拮抗剂可减少 消耗蔗糖溶液。该项目旨在进一步探索 这些发现并检验了阿片类药物系统在 腹侧纹状体可能尤其涉及享乐性和 摄食行为背后的关联机制。我们的三个具体目标 目标是：(1)对以下物质的作用进行药理学分析 伏隔核和其他核团内的阿片受体亚型 高度可口的糖精对纹状体部位的奖励作用 解决方案。(Ii)对动机进行行为分析 阿片类药物操作伏隔核所致的状态。几个 将利用行为范式，包括对甜蜜的反应 按累进比率时间表奖励，有条件的增援， T型迷宫中的离散试验学习和先前大鼠的饮食选择 选择用于基线饮食偏好的特定模式。(Iii) 条件性摄食反应的发育和表达分析 这是伏隔核反复暴露于鸦片类药物的结果。 所有这些实验的共同方法是利用直接 脑内微量注射阿片激动剂和拮抗剂 有特定的行为模式。这些实验的结果可能 有助于我们对大脑腹侧纹状体的理解 加固过程。

Opiates, such as heroin and morphine, constitute one of the major classes of abused drugs in the world. Although the treatment of opiate addiction remains problematic, enormous advances have been made in our general understanding of the systems on which these drugs act in the brain. The endogenous opioids are believed to play a major role in diverse biological processes such as pain modulation, affect and emotion, response to stress, and reinforcement. One major area of research has focused on opioid mediation of feeding and drinking. A hypothesis that has received considerable support states that opioids specifically regulate the rewarding or hedonic aspects of food. Moreover, clinical findings suggest that dysfunction of opioids may in some way be linked to human disorders characterized by excessive cravings, impulsive behavior and loss of control, much as in bulimia and alcoholism. In the past several years, our laboratory has investigated the effects of opioid manipulations of the nucleus accumbens on feeding behavior. This brain structure, part of the ventral striatum, is thought to be a critical substrate for the reinforcing effects of opiate and psychostimulant drugs. Our research to date has shown that microinjection of morphine into the nucleus accumbens results in a striking increase in feeding behavior and excessive food intake. This effect has been shown to be primarily mu-receptor mediated and anatomically localized to ventral, limbic-afferented striatal regions. Moreover, conditioned feeding develops following control or sham injections in animals that have received repeated microinjections of morphine. Injection of an opiate antagonist into this region reduces consumption of a sucrose solution. This project aims to further explore these findings and to test the hypothesis that opioid systems in the ventral striatum may be particularly involved in the hedonic and associative mechanisms underlying ingestive behavior. Our three specific objectives are: (i) To conduct a pharmacological analysis of the role of specific opiate receptor subtypes within the nucleus accumbens and other striatal sites in the rewarding effects of a highly palatable saccharin solution. (ii) To carry out a behavioral analysis of the motivational state induced by opioid manipulation of the nucleus accumbens. Several behavioral paradigms will be utilized including responding for sweet reward on a progressive ratio schedule, conditioned reinforcement, discrete-trial learning in a T-maze, and diet selection in rats previously selected for specific patterns of baseline diet preferences. (iii) To analyze the development and expression of the conditioned feeding response that results from repeated exposure of the nucleus accumbens to opiates. The approach common to all these experiments is the utilization of direct brain microinjection of opioid agonists and antagonists in conjunction with specific behavioral paradigms. The outcome of these experiments may contribute to our understanding of the ventral striatum in brain reinforcement processes.