GLUTAMATERIC MECHANISMS OF DRUG-CONDITIONED BEHAVIOR

描述（由申请人提供） 众所周知，学习在发展中起着重要的作用。 和维持药物成瘾。动物模型已经成功地用于 运用操作性原则， 经典条件作用该项目旨在开发一种更好的 理解经典条件反射的神经行为基础 滥用药物的行为影响。我们假设， 神经传递在这些条件过程中起关键作用。调节 由位于彼得堡的巴甫洛夫医科大学的科学家开发的模型 将在他们的实验室里进行研究， 假设和评价谷氨酸拮抗剂作为可能药物治疗 药物依赖具体而言，谷氨酸受体拮抗剂的能力， 受滥用药物（吗啡、可卡因）影响的行为将 在啮齿动物中评估。作用于N-甲基-D-天冬氨酸（NMDA）亚型的拮抗剂 将检测谷氨酸受体。具体目标是：1）研究 位点选择性NMDA受体拮抗剂对药物消退的影响-与 非药物条件行为;和2）估计NMDA受体的作用， 发展和表现的禁欲后增加药物消费。 拟议的研究将补充该项目前几年所做的工作 与各种位点选择性谷氨酸受体拮抗剂在广泛的 实验模型包括药物调节的不同方面， 如：1）药物条件激活自发活动，2） 条件刺激对颅内自我刺激的易化作用 与滥用药物或奖励脑电刺激有关，3） 通过使用静脉内药物的条件反射维持反应 自我给药程序; 4）药物耐受性的条件成分， 依赖性;和5）戒断后药物消费的增加。

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.