Social and Enviromental Influences on Opioid Sensitivity

描述(由申请人提供)：本申请是对NOT-OD-09-058的回应：美国国立卫生研究院宣布恢复法资金可用于竞争性修订申请。药物滥用研究的一个主要组成部分涉及确定导致个人出现药物滥用和依赖问题的可能性的社会和环境变量。在这项申请的父母拨款(2R15DA014255)中，我们提出了一系列研究，考察社会和环境丰富对药物自我管理措施的影响。这些研究即将完成，我们在这里报告了青春期社会和环境的丰富降低了雌性大鼠对低剂量可卡因的反应。药物自我给药的动物模型面临的一个问题是，在测试过程中，受试者必须离开家庭环境。因此，社会接触的直接影响不能用静脉给药的药物自我给药措施来检验。这代表了动物模型的显著局限性，因为人类的药物使用通常发生在他人在场的情况下，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费。通过对我们现有的操作调节室进行一些简单的修改，我们可以建造一个巨大的自我给药室，它也可以作为两只大鼠的家笼。利用这个小室，我们可以在另一只大鼠持续给药的情况下，检查个别大鼠的药物自我给药情况。重要的是，这种安排允许我们比较一只有同伴也可以自由接触毒品的动物(即共同使用者)和一只有同伴但不能接触毒品的动物(即戒毒者)。这个项目的主要目的是检查隔离和社会安置的大鼠的可卡因自我管理，但重要的警告是，社会安置的受试者将每天24小时一起生活在同一个笼子里，包括在每天的自我管理期间。作为一种新的操作，我们将检验有一个自我管理可卡因的同伴和一个不自我管理可卡因的同伴的效果。该项目的最终目标是在雄性和雌性大鼠身上检查这些操作，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。 与公共卫生有关：青春期标志着发展的关键时期，个人在这一时期特别容易出现药物滥用和依赖问题。使用动物模型，我们将检验与有接触毒品的同伴(即共同使用者)和不接触毒品的同伴(即戒毒者)的社会接触对青春期大鼠可卡因自我管理的影响。我们将考察男性和女性的这些影响，以确定社会接触对寻求毒品行为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.