Reference-dose method and cocaine-conditioned choice

参考剂量方法和可卡因条件选择

基本信息

批准号：
7046836
负责人：
Rick A Bevins
金额：
$ 7.1万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2008-03-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7046836
关键词：
association learning behavioral /social science research tag cocaine cognition conditioning craving dopamine antagonists dosage drug abuse laboratory rat neurobiology substance abuse related behavior toxicology

项目摘要

DESCRIPTION (provided by applicant): Research supports the assumption that associative learning processes contribute to acquisition, maintenance, and/or relapse of habitual drug-taking patterns. One preclinical animal model that has contributed importantly to understanding these conditioned associations is the cocaine place-conditioning preparation in rats. In a "standard" place-conditioning experiment, one distinct environment is repeatedly paired with cocaine administration; a second environment is equally experienced without cocaine. In a later drug-free test, rats given free access to both environments will spend more time in the cocaine-paired environment indicating that the paired environment has acquired rewarding value that controls approach/drug-seeking behaviors. Unfortunately, this widely used method is relatively insensitive to such variables as changes in cocaine dose (i.e., conditioned preference tends to be all-or-none) thus limiting its usefulness for a more detailed examination of processes mediating drug-seeking behavior. The main goal of the research in this proposal is to systematically assess the utility of a modified version of the standard protocol that overcomes some of these limitations. This new method, termed "reference-dose procedure," provides a known cocaine conditioning history in both environments (cf. standard protocol only conditions one environment). The following Aims will be used to obtain this goal. Specific Aim 1 will assess the change in choice behavior that occurs when varying doses of cocaine paired with one environment (e.g., 0.1, 0.3, 0.45, 0.6, 0.9, or 1.2) compete with another environment paired with a moderate or low reference-dose of cocaine (i.e., establish dose-effect curves). Specific Aim 2 will determine the extent to which the reference-dose method increases the sensitivity of the place conditioning procedure to antagonism using the dopamine D1 receptor antagonist SCH-23390. This research will provide the requisite foundation for this more sensitive reference-dose method. In doing so, new research into basic cognitive, behavioral, and neurobiological processes mediating drug-conditioned choice behavior will become possible. That research could translate into more effective intervention strategies.

描述（由申请人提供）：研究支持以下假设：关联学习过程有助于习惯性吸毒模式的获取，维护和/或复发。有助于理解这些条件关联的一种临床前动物模型是大鼠可卡因的位置调节制剂。在“标准”位置调节实验中，一个不同的环境与可卡因给药反复配对。没有可卡因的第二个环境同样经历。在以后的无药物测试中，可以自由进入这两个环境的大鼠将在可卡因配对的环境中花费更多的时间，这表明配对环境已经获得了控制方法/寻求吸毒行为的奖励价值。不幸的是，这种广泛使用的方法对可卡因剂量的变化（即条件偏好倾向于全有或无人）的变量相对不敏感，从而限制了其对介导毒品行为的过程的更详细检查的有用性。该提案中研究的主要目标是系统地评估克服这些限制的标准协议的修改版本的实用性。这种新方法称为“参考剂量过程”，在这两个环境中提供了已知的可卡因调节历史（参见标准协议仅条件一个环境）。以下目标将用于获得此目标。当可卡因与一种环境（例如0.1、0.3、0.45、0.6、0.9或1.2）配对时，特定目标1将评估选择行为的变化，而可卡因剂量的剂量会发生变化。特定的目标2将确定参考剂量方法使用多巴胺D1受体拮抗剂SCH-23390提高位置调节程序对拮抗的敏感性的程度。这项研究将为这种更敏感的参考剂量方法提供必要的基础。在此过程中，将成为可能的基本认知，行为和神经生物学过程的新研究，介导药物条件的选择行为将成为可能。这项研究可以转化为更有效的干预策略。