Behavioral Factors in Drug Tolerance

药物耐受性的行为因素

• 批准号: 6666545
• 负责人: MARC N BRANCH
• 金额: $ 0.44万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6666545
• 关键词: Behavioral; Factors; Drug; Tolerance

DESCRIPTION (provided by applicant): The general significance of the proposed research is that it may have relevance to the development of dependence on cocaine. Cocaine use and dependence remain significant health issues in the United States. For example, recent surveys indicated that more than 5.6 million Americans had used cocaine within the past year, and that more than 23 million have taken the drug at some time in their lifetimes. Interestingly, estimates indicate that only about 5 to 10% of those who use cocaine eventually become dependent on it. It appears, therefore, that cocaine tends not to be immediately addictive. The factors that lead to dependence have not been identified, but clinical evidence suggests that a prolonged period of intermittent use of the drug often precedes the development of dependence. The proposed research is aimed at furthering our knowledge concerning behavioral effects of relatively long-term intermittent exposure to cocaine. Laboratory study of effects of long-term intermittent exposure to cocaine has yielded a puzzling array of results. Sometimes tolerance is observed, sometimes sensitization. Previous investigations, however, have indicated that experiential/behavioral factors can determine whether or not tolerance or sensitization occurs to cocaine's effects. The proposed research is aimed at adding to our knowledge of how experiential factors interact with repeated cocaine exposure. The specific research aims of this application are to: 1.) Expand our analyses of the interaction between explicitly conditioned operant behavior (as a model of purposive behavior) and general activity during repeated exposure to cocaine. Our recent finding that presence of an operant contingency prevented the observation of sensitization to the drug's effects on general activity has set the basis for this aim. 2.) Continue to examine the role of alterations in rate of reinforcement as a predictor of tolerance to effects of cocaine. 3) Continue analyses of reinforcement-schedule-parameter dependent tolerance. We plan to determine if such tolerance is "contingent," if and how it is related to behavioral economic factors, and how rate of reinforcement and ratio contingencies interact. This application is to provide support for the PI so that he may devote at least 75% of his time to research on the foregoing issues. The study of long-term, intermittent exposure to cocaine has potential relevance to the genesis of cocaine dependence. Understanding of the processes that occur under long-term, intermittent exposure should facilitate the development of effective treatment and, especially, prevention programs.

描述（由申请人提供）：拟议研究的一般意义在于它可能与可卡因依赖的发展有关。可卡因的使用和依赖仍然是美国的重大健康问题。 例如，最近的调查表明，超过 560 万美国人在过去一年内吸食过可卡因，超过 2300 万美国人在一生中的某个时候吸过这种药物。 有趣的是，据估计，只有约 5% 至 10% 的可卡因使用者最终会对它产生依赖。 因此，可卡因似乎不会立即让人上瘾。 导致依赖性的因素尚未确定，但临床证据表明，长时间间歇性使用该药物往往会先于依赖性的发展。 拟议的研究旨在加深我们对相对长期间歇性接触可卡因的行为影响的了解。 对长期间歇性接触可卡因影响的实验室研究得出了一系列令人费解的结果。 有时观察到耐受性，有时观察到敏化。 然而，先前的研究表明，经验/行为因素可以决定是否对可卡因的作用产生耐受或过敏。 拟议的研究旨在增加我们对经验因素如何与反复接触可卡因相互作用的了解。 该应用程序的具体研究目标是： 1.) 扩展我们对重复接触可卡因期间的明确条件操作行为（作为有目的行为的模型）与一般活动之间相互作用的分析。 我们最近的发现是，操作性意外事件的存在阻碍了观察药物对一般活动的影响，这为这一目标奠定了基础。 2.) 继续研究强化率的变化作为可卡因耐受性预测指标的作用。 3) 继续分析强化-时间表-参数相关的容差。 我们计划确定这种容忍度是否是“偶然的”，它是否与行为经济因素相关以及如何相关，以及强化率和比率意外事件如何相互作用。 本申请旨在为PI提供支持，使其能够投入至少75%的时间来研究上述问题。 对长期、间歇性接触可卡因的研究与可卡因依赖的起源具有潜在的相关性。了解长期、间歇性暴露下发生的过程应有助于制定有效的治疗方案，特别是预防方案。