Social and Enviromental Influences on Opioid Sensitivity

描述（由申请人提供）：药物滥用研究的一个主要组成部分包括确定导致受试者群体药物敏感性差异的各种生物学、药理学和环境因素。现有文献描述了这些差异的许多例子，并确定了几个促成变量。对成瘾药物的敏感性产生强烈影响的一组因素是受试者的社会和环境历史。在我们最初的AREA应用中，我们提出了一系列研究，研究社会和环境富集是否会影响雄性大鼠对阿片类药物的抗痛觉性和奖励效应的敏感性。这些研究已经完成，在本应用程序中，我们报告了富集的大鼠比分离的大鼠对阿片类药物的影响更敏感，并且这些影响在低功效阿片类药物测试时最为明显。这些发现表明，阿片受体系统对社会和环境的操纵是敏感的，而这些操纵对阿片受体激动剂的敏感性具有功能性后果。在这一竞争性更新中，我们建议在两个药物寻求行为的动物模型中，即条件位置偏好过程和药物自我给药过程中，研究社会和环境操纵对阿片类药物和可卡因敏感性的影响。作为一项新的研究，我们计划研究社会和环境对男性和女性受试者的影响，并确定性腺激素是否影响这些影响。最后，我们还提出了一个新的研究路线，检查有氧运动对药物寻求行为的影响，确定性激素是否影响男性和女性受试者的这些影响。这些研究应确定导致受试者群体中药物寻求行为差异的关键生物学、药理学和环境因素。

DESCRIPTION (provided by applicant): A major component of drug abuse research involves identifying the various biological, pharmacological and environmental factors that contribute to differences in drug sensitivity across subject populations. The existing literature describes numerous examples of these differences and several contributing variables have been identified. One set of factors that exerts a strong influence on sensitivity to the effects of addictive drugs is the social and environmental history of the subject. In our original AREA application, we proposed a series of studies examining whether social and environmental enrichment influences sensitivity to the antinociceptive and rewarding effects of ¿ opioids in male rats. Those studies have been completed, and in this application we report that enriched rats are more sensitive than isolated rats to the effects of ¿ opioids, and that these effects are most apparent when lower efficacy opioids are tested. These findings suggest that the ¿ opioid receptor system is sensitive to social and environmental manipulations, and that these manipulations have functional consequences for sensitivity to the effects of ¿ opioid agonists. In this competitive renewal, we propose to examine the effects of social and environmental manipulations on sensitivity to opioids and cocaine in two animal models of drug-seeking behavior, the conditioned place preference procedure and the drug self-administration procedure. As a novel line of investigation, we plan to examine the effects of social and environmental enrichment in both male and female subjects, and to determine whether gonadal hormones influence these effects. Finally, we also propose a novel line of studies examining the effects of aerobic exercise on drug-seeking behavior, determining whether gonadal hormones influence these effects in male and female subjects. These studies should identify the critical biological, pharmacological and environmental factors contributing to differences in drug-seeking behavior across subject populations.