BRAIN STIMULATION MODELS OF DRUG ABUSE

描述（由申请人提供）： 这项科学家奖的主要长期目标是进行研究，比较年轻和老年大鼠对阿片类药物和可卡因的反应。初步数据表明，年轻大鼠和老年大鼠之间的奖励机制存在重大差异。随着人口老龄化，药物依赖的老年人人数可能急剧增加;然而，老龄化中的药物滥用问题在很大程度上被忽视。有相当多的证据表明，随着年龄的增长，与滥用物质的享乐效应有关的大脑系统发生了变化。拟议研究的一个主要方面将使用一些滥用物质的奖励作用的动物模型来检查这些改变的功能后果。具体而言，研究的滥用物质将是吗啡、海洛因和可卡因，以及改变相关神经递质系统的特定物质，这些神经递质系统被认为与这些滥用物质的奖励效应有关。实验动物为大鼠，具体使用的模型为药物自我给药、条件性位置偏爱和脑刺激奖励。此外，还将研究特异性多巴胺（DA）激动剂GBR 12009。在单独和联合给予吗啡、GBR 12909和BSR后，将在老年和年轻动物中使用体内微透析测量丘脑核内的DA。另一个领域或研究将实验性地研究大脑中的基础变化，所述基础变化是由先前在大鼠饮酒期间与酒精相关的环境线索的呈现而促成的。该模型将利用定量2-脱氧葡萄糖（（2-DG））自动放射照相方法来确定葡萄糖代谢的局部大脑代谢率。除了研究实验之外，还建议对滥用物质研究中使用的行为方法进行历史回顾。

DESCRIPTION (provided by applicant): The major long-term objective of this scientist award is to conduct research comparing young and old rat's response to opiates and cocaine. Preliminary data has suggested major differences in reward mechanisms between young and old rats. As the population grows older the number of elderly individuals with drug dependence may sharply increase; the issue, however, of drug abuse in aging has, for the most part, been ignored. There is considerable evidence that with aging there are alterations in the brain systems implicated in the mediation of the hedonic effects of abused substances. A major aspect of the proposed research will examine the functional consequences of these alterations using a number of animal models of the rewarding effects of abused substances. Specifically the abuse substances studied will be morphine, heroin and cocaine as well as specific substances that alter the relevant neurotransmitter systems that are believed involved in the rewarding effects of these abused substances. The experimental animal will be the rat and the specific models used will be drug self-administration, conditioned place preference, and brain stimulation reward. In addition the specific dopamine (DA) agonist GBR 12009 will be investigated. DA within the nucleus accumbens will be measured using in vivo micro-dialysis in aged and young animals following the administration of morphine, GBR 12909 and BSR, alone and in combination. Another area or research will to experimentally investigate basal changes in the brain that are precipitated by the presentation of environmental cues that previously had been associated with alcohol during drinking bouts in rats this model will make use of the quantitative 2-deoxy-glucose ((2-DG) Auto radiographic method of determining local cerebral metabolic rate of glucose metabolism. In addition to the research experiments it is proposed to write a historical review of the behavioral methods that have been used in the study of abused substances.