Social and Enviromental Influences on Opioid Sensitivity

描述（由申请人提供）：此申请是对NOT-OD-09-058的回应：NIH宣布为竞争性修订申请提供恢复法案资金。药物滥用研究的一个主要组成部分涉及确定导致个人产生药物滥用和依赖问题的可能性的社会和环境变量。在本申请的家长资助（2R15DA014255）中，我们提出了一系列研究，考察社会和环境富集对药物自我给药措施的影响。这些研究即将完成，在这里我们报告说，在青春期的社会和环境丰富减少了雌性大鼠低剂量可卡因维持的反应。动物自我给药模型面临的一个问题，特别是那些研究社会和环境操纵的动物模型，是在测试期间必须将受试者从家庭环境中移除。因此，社会接触的直接影响不能通过静脉给药的自我给药措施来检验。这代表了动物模型的一个重大局限性，因为人类的药物使用通常是在其他人在场的情况下发生的，而这些其他人的行为（即，他们是否也在使用药物）可以反馈影响个人的药物消耗。通过对我们现有的操作性条件反射室进行一些简单的修改，我们可以建造一个大型的自我管理室，也可以作为两只老鼠的家庭笼子。利用这个实验室，我们可以在另一只大鼠连续出现的情况下，检查单个大鼠的药物自我给药情况。重要的是，这种安排使我们能够比较动物的药物自我管理，即有一个同伴也可以自由获得药物（即共同使用者）与有一个同伴不能获得药物（即戒酒者）的动物。该项目的主要目的是检查隔离和社会饲养的大鼠的可卡因自我给药，重要的警告是，社会饲养的受试者将每天24小时生活在同一个笼子里，包括每天的自我给药期间。作为一种新颖的操作，我们将检查有一个自我服用可卡因的同伴与有一个不自我服用可卡因的同伴的影响。该项目的最终目的是在雄性和雌性大鼠中检查这些操作，以确定社会接触对药物自我给药措施的影响是否存在性别差异。

DESCRIPTION (provided by applicant): This application is in response to NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. A major component of drug abuse research involves identifying the social and environmental variables that contribute to an individual's likelihood of developing problems with substance abuse and dependence. In the parent grant to this application (2R15DA014255), we proposed a series of studies examining the effects of social and environmental enrichment on measures of drug selfadministration. Those studies are nearing completion, and here we report that social and environmental enrichment during adolescence decreases responding maintained by a low dose of cocaine in female rats. One problem facing animal models of drug self-administration, especially those examining social and environmental manipulations, is that subjects must be removed from the home environment during testing. Consequently, the immediate effects of social contact cannot be examined on measures of drug self-administration that employ intravenous drug delivery. This represents a significant limitation of animal models, as drug use in humans typically occurs in the presence of others, and the behavior of these other people (i.e., whether or not they are also using drugs) can feedback to influence the drug consumption of the individual. With a few simple modifications to our existing operant conditioning chambers, we can construct a large selfadministration chamber that can also serve as a home cage for two rats. Using this chamber, we can examine drug self-administration in individual rats under conditions in which another rat is continuously present during drug self-administration sessions. Importantly, this arrangement allows us to compare drug self-administration in an animal that has a companion that also has free access to drugs (i.e., a co-user) versus an animal that has a companion without access to drugs (i.e., an abstainer). The primary aim of this project is to examine cocaine self-administration in isolated and socially housed rats, with the important caveat that the socially housed subjects will be living together in the same cage 24 hr/day, including during daily self-administration sessions. As a novel manipulation, we will examine the effects of having a companion that self-administers cocaine versus having a companion that does not self-administer cocaine. A final aim of this project is to examine these manipulations in both male and female rats to determine whether there are sex differences in the effects of social contact on measures of drug self-administration. PUBLIC HEALTH RELEVANCE: Adolescence marks a critical period in development in which individuals are particularly vulnerable to developing problems with substance abuse and dependence. Using an animal model, we will examine the effects of social contact with a companion with access to drugs (i.e., a co-user) versus without access to drugs (i.e., an abstainer) on cocaine self-administration in adolescent rats. We will examine these effects in both males and females to determine whether there are sex differences in the effects of social contact on drug-seeking behavior.