GLUTAMATERIC MECHANISMS OF DRUG-CONDITIONED BEHAVIOR

描述(由申请人提供) 众所周知，学习在人的发展中起着重要的作用 以及维持吸毒成瘾。动物模型已经成功地应用于 运用运筹学原理对这些学习现象进行分离和研究 经典条件反射。这个项目的重点是开发更好的 对经典条件反射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性过程中起着关键作用。条件反射 圣彼得堡巴甫洛夫医科大学科学家开发的模型 将在他们的实验室中用于进行研究，以评估这一点 假设和评估谷氨酸拮抗剂可能的药物治疗 药物依赖。具体地说，谷氨酸受体拮抗剂能够 以滥用药物(吗啡、可卡因)为条件的情感行为将 在啮齿动物身上进行评估。作用于N-甲基-D-天冬氨酸(NMDA)亚型的拮抗剂 将对谷氨酸受体进行测试。具体目的是：1)学习 位点选择性NMDA受体拮抗剂对药物消退的影响。 非药物条件性行为；以及2)估计NMDA受体在 戒毒后药物消费增加的发展和表现。 拟议的研究将补充该项目早些年所做的工作 与各种部位选择性谷氨酸受体拮抗剂在广泛的 包含药物调节的不同方面的实验模型 AS：1)药物条件激活的运动活动，2) 条件刺激对脑内自我刺激的易化作用 与滥用药物或奖励大脑电刺激有关，3) 静脉注射药物维持条件增强剂的反应 自我给药程序；4)药物耐受性的条件性成分和 依赖；5)戒毒后的药物消费增加。

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.