Effects of Negative Consequences on Drug Self Administration in Rats

负面后果对大鼠自我给药的影响

• 批准号: 7641471
• 负责人: Jerry B Richards
• 金额: $ 23.05万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7641471
• 关键词: Address; Affective; Animal Model; Animals; Behavioral; Cocaine; Cognitive; Consumption; Development; Diagnostic and Statistical Manual of Mental Disorders; Dose; Drug Addiction; Drug abuse; Drug usage; Goals; Human; Human Characteristics; Impulsivity; Individual; Individual Differences; Injection of therapeutic agent; Intake; Knowledge; Laboratories; Laboratory Animal Models; Measures; Mediating; Modeling; Outcome; Pharmaceutical Preparations; Play; Predisposition; Procedures; Process; Psychological reinforcement; Punishment; Rattus; Regulation; Reinforcement Schedule; Research; Resistance; Rewards; Rodent Model; Schedule; Self Administration; Shock; Stimulus; Uncertainty; Water; Wit; Work; drug abstinence; drug efficacy; neurobiological mechanism; public health relevance; reinforcer; research study; response; reward processing; role model; tool

DESCRIPTION (provided by applicant): The primary objective of the proposed research is to develop a rodent model of self administration (SA) in which drug consumption has delayed negative consequences. Self administration procedures in which the animals make responses that are reinforced by IV drug injections are widely used and are perhaps the most convincing non-human animal models of drug abuse. Non-human animal SA models, however, may not model important aspects of human drug SA. In humans, impulsivity is considered an important component of drug abuse because individuals take drugs despite the knowledge of negative (often delayed) outcomes associated with drug use. In contrast, standard laboratory animal models of SA have no explicit negative outcomes associated with the SA of the drug. Because there are currently no SA models that incorporate negative consequences, the impact of negative outcomes is not generally incorporated into current ideas about the underlying behavioral and neurobiological mechanisms mediating drug abuse. The goal of the Experiment 1 of this application is to determine a dose of cocaine and an amount of water that have equivalent reinforcing efficacy. In this application reinforcing efficacy is measured using progressive ratio schedules of reinforcement. In progressive ratio schedules, reinforcement efficacy is operationally defined as the break point (BP) which indicates the maximum number of responses an animal will make on a progressive ratio schedule of reinforcement for a given reinforcer. Determination of a dose of cocaine and an amount of water that have equivalent efficacy will insure that cocaine and water reinforcers of equivalent reinforcing efficacy are used In Experiments 2 and 3. Experiment 2 will determine if immediate shock has different effects on the reinforcing efficacy of drug and natural reinforcers using the progressive ratio schedule of reinforcement. Building upon Experiments 1 and 2, Experiment 3 will determine the effects of delaying the shock on the reinforcing efficacy of the cocaine/shock and water/shock reinforcers. These studies will advance to our understanding of drug abuse by determining if punishment or delays to punishment have similar (or dissimilar) effects on drug (cocaine) and natural (water) reinforcers of equivalent reinforcing efficacy. These results will help to determine if a "punished" SA model is a valuable tool with which to investigate the behavioral and cognitive regulation of drug abuse by negative consequences. PUBLIC HEALTH RELEVANCE: The primary objective of the proposed research is to develop a rodent model of self administration (SA) in which drug consumption has delayed negative consequences. There is little doubt that non-human animal SA procedures model important aspects of drug taking in humans; however in some respects the typical application of this model in the laboratory does not model important aspects of drug consumption by human addicts. According to the Diagnostic and Statistical Manual of Mental Disorders (APA, 1994) an important characteristics of human drug addiction is continued drug intake despite harmful consequences. However, current non human animal models of drug abuse do not address this important issue. Consequently, the impact of negative outcomes is not generally incorporated into current ideas about the underlying behavioral and neurobiological mechanisms mediating drug abuse. We believe that drug abuse in humans is a function of two separate processes, "rewarding" positive affective responses to the drug and "impulsivity-related" factors, or influences that normally inhibit or limit the use of drugs. Development of a non human SA model that incorporates negative consequences will enhance research into "impulsivity-related factors" that are necessary for drug abstinence.

描述(由申请人提供)：拟议研究的主要目标是发展一种自我给药(SA)的啮齿动物模型，在该模型中，药物消费延迟了负面后果。动物通过静脉注射药物来做出反应的自我给药程序得到了广泛的应用，可能是最令人信服的非人类药物滥用动物模型。然而，非人类动物SA模型可能不会模拟人类药物SA的重要方面。在人类中，冲动被认为是药物滥用的一个重要组成部分，因为尽管知道与药物使用相关的负面结果(通常是延迟的)，但个人仍然服用药物。相比之下，标准的SA实验动物模型没有与药物SA相关的明确的负面结果。因为目前还没有包含负面结果的SA模型，所以负面结果的影响通常不会被纳入到目前关于药物滥用的潜在行为和神经生物学机制的想法中。此应用程序的实验1的目标是确定具有同等增强效果的可卡因剂量和水的量。在此应用中，使用钢筋的累进比率计划来衡量加固效果。在累进比例表中，增强效果在操作上被定义为断点(BP)，它指示动物在给定增强剂的累进比例表上做出的最大反应数。确定同等效力的可卡因和水的剂量将确保在实验2和3中使用同等增强效果的可卡因和水增强剂。实验2将使用增强剂的累进比率表来确定即刻休克对药物和天然增强剂的增强效果是否有不同的影响。在实验1和实验2的基础上，实验3将确定延迟休克对可卡因/休克和水/休克增强剂强化效果的影响。这些研究将通过确定惩罚或延迟惩罚对具有同等增强效果的药物(可卡因)和天然(水)增强剂是否具有相似(或不同)影响，从而促进我们对药物滥用的理解。这些结果将有助于确定“惩罚的”SA模型是否是通过负面后果来研究药物滥用的行为和认知调节的有价值的工具。公共卫生相关性：拟议研究的主要目标是开发一种自我给药(SA)的啮齿动物模型，在该模型中，药物消费推迟了负面后果。毫无疑问，非人类动物SA程序模拟了人类吸毒的重要方面；然而，在某些方面，该模型在实验室中的典型应用并不模拟人类吸毒者吸毒的重要方面。根据《精神疾病诊断和统计手册》(《精神疾病诊断和统计手册》，1994年)，人类吸毒成瘾的一个重要特征是不顾有害后果持续吸食毒品。然而，目前的非人类药物滥用动物模型并没有解决这个重要的问题。因此，负面结果的影响通常没有被纳入目前关于调节药物滥用的潜在行为和神经生物学机制的想法中。我们认为，人类的药物滥用是两个不同过程的函数，对药物的积极情感反应和“冲动相关”因素，即通常抑制或限制药物使用的影响，“奖励”。开发一个包含负面后果的非人类SA模型，将加强对戒毒所必需的“冲动相关因素”的研究。