GLUTAMATERIC MECHANISMS OF DRUG-CONDITIONED BEHAVIOR

药物调节行为的谷氨酸机制

• 批准号: 6622189
• 负责人: ROBERT L BALSTER
• 金额: $ 2.88万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622189
• 关键词: Commonwealth of Independent States; NMDA receptors; behavioral /social science research tag; behavioral habituation /sensitization; behavioral medicine; brain electronic stimulator; cocaine; conditioning; cooperative study; drug abuse; drug abuse chemotherapy; drug adverse effect; electrodes; inhibitor /antagonist; intravenous administration; laboratory rat; morphine; neuropsychological tests; nucleus accumbens; operant conditionings; phencyclidine; psychological reinforcement; reinforcer; self medication; self stimulation; sweetening agents

DESCRIPTION (provided by applicant) It is well established that learning plays an important role in the development and maintenance of drug addictions. Animal models have been successfully used to isolate and study these learning phenomenon using principles of operant and classical conditioning. This project is focused on developing a better understanding of the neurobehavioral basis for classically conditioned behavioral effects of drugs of abuse. We hypothesize that glutamatergic neurotransmission plays a key role in these conditioned processes. Conditioning models developed by scientists at Pavlov Medical University in St. Petersburg will be used in their laboratories to conduct research to evaluate this hypothesis and evaluate glutamate antagonists as possible pharmacotherapies for drug dependence. Specifically, the ability of glutamate receptor antagonists to affect behaviors conditioned with drugs of abuse (morphine, cocaine) will be assessed in rodents. Antagonists acting at N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors will be tested. The specific aims are to: 1) study effects of site-selective NMDA receptor antagonists on extinction of drug- vs. non-drug conditioned behaviors; and 2) estimate the role of NMDA receptors for the development and expression of post-abstinent increase in drug consumption. The proposed studies will complement work done in earlier years of this project with various site-selective glutamate receptor antagonists in a wide range of experimental models encompassing different aspects of drug conditioning such as: 1) the drug-conditioned activation of locomotor activity, 2) the facilitation of intracranial self-stimulation induced by conditioned stimuli associated with abused drugs or rewarding electrical brain stimulation, 3) the responding maintained by conditioned reinforcers using intravenous drug self-administration procedures; 4) conditioned components of drug tolerance and dependence; and 5) post-abstinent increase in drug consumption.

描述（由申请人提供） 众所周知，学习在发展中起着重要作用 和吸毒成瘾的维持。动物模型已成功使用 使用操作方和 经典条件。该项目的重点是开发更好 对经典条件的神经行为基础的理解 滥用药物的行为影响。我们假设谷氨酸能 神经传递在这些条件过程中起关键作用。调理 由科学家在圣彼得堡的帕夫洛夫医科大学开发的模型 将在其实验室中使用研究来评估这一点 假设和评估谷氨酸拮抗剂作为可能的药物疗法 药物依赖。具体而言，谷氨酸受体拮抗剂的能力 用滥用药物（吗啡，可卡因）调节的行为将是 通过啮齿动物进行评估。作用于N-甲基-D-天冬氨酸（NMDA）亚型的拮抗剂 将测试谷氨酸受体。具体目的是：1）研究 位点选择性NMDA受体拮抗剂对药物灭绝的影响。 非毒品条件行为； 2）估计NMDA受体的作用 药物消费量增加后的发展和表达。 拟议的研究将补充该项目早期所做的工作 具有各种位点选择性谷氨酸受体拮抗剂 实验模型包括药物调节的不同方面 AS：1）运动活性的药物条件激活，2） 促进条件刺激引起的颅内自刺激 与滥用药物或奖励电脑刺激相关，3） 使用静脉注射药物的条件增强剂维护的响应 自我管理程序； 4）药物耐受性的条件成分和 依赖； 5）药物消耗后侵入后增加。