DRUGS OF ABUSE AND BRAIN STIMULATION REWARD IN THE MOUSE

描述(由申请人提供)：近年来， 对吸毒者特征的研究集中在脆弱性上， 遗传学在这种脆弱性中可能扮演的角色，以及分子 毒品使用和复发的机制的基础。固有的 对这些问题的理解就是对机制的理解 参与滥用物质对大脑奖赏系统的作用(S)。 然而，在很大程度上，研究人员利用老鼠作为动物 作为研究的选择，而大多数关于遗传差异的实验都使 以小鼠为实验动物。在试图调查这一行为时 在这些基因突变中，研究人员主要依赖于简单的 无条件的行为。拟议的研究旨在适应 测量脑刺激奖赏(BSR)变化的小鼠技术 已经在老鼠身上成功地使用了。程序是1)离散的 测量BSR阈值的试验、非速率、心理物理方法 和2)一个平行的程序，测量动物的参与能力 通过测量对来自 同样的大脑部位。除了测量刺激阈值，潜伏期 还测量了响应的大小。因此，这些技术允许确定 不仅是奖励制度的变化，而且这些变化是否 被运动和注意力因素搞混了。拟议中的实验将 探索CB57/B6和D对吗啡和可卡因反应的差异，以及 DAT缺陷突变小鼠。这些程序在小鼠身上的成功开发 将允许对特定表型的性质有更具体的了解 这可能与人类的状况有关。

DESCRIPTION (provided by applicant): In recent years a Major thrust in the study of the characteristics of the drug abuser has focused on vulnerability, the possible role that genetics play in this vulnerability, and the molecular underpinnings of the mechanisms of use and relapse into drug use. Intrinsic to the understanding of these problems is the understanding of the mechanisms involved in the action of the abused substances on the brain reward system(s). However, for the most part, researchers have made use of the rat as the animal of choice for study, while most of the experiments on genetic differences make use of mouse as the experimental animal. In trying to investigate the behavior of these genetic mutations investigators have relied mostly on simple unconditioned behavior. The proposed research is designed to adapt for the mouse techniques for measuring the changes in brain-stimulation reward (BSR) that have been successfully used in the rat. The procedures are 1) a discrete trial, rate independent, psychophysical method for measuring the BSR threshold and 2) a parallel procedure that measures the ability of the animal to attend to a stimulus by measuring the detection of non-rewarding stimulation from the same brain site. In addition to measuring the stimulation thresholds, latency of response is also measured. Thus the techniques allow for the determination of not only changes in the reward system but also whether these changes are confounded by motor and attention factors. The proposed experiments will explore differences in response to morphine and cocaine in CB57/B6 and D, and DAT deficient mutant mice. Successful development of these procedures in mice will allow a more specific understanding of the nature of specific phenotypes that may have relationships to the human condition.