Mechanisms of Opiate and Stimulant Drug Reinforcement

描述(由申请人提供)：该项目的主要长期目标是了解有助于鸦片类药物和兴奋剂滥用的自我管理的神经机制。将应用行为药理学方法来解决三个具体目标，每个目标都建立在本项目头十四年期间开展的工作的基础上和/或扩展。它们是：1)将引发药物寻求行为的潜在动机过程与药物自我管理所激活的强化过程分开；2)继续并扩大对药物滥用行为“复发”所涉及的机制的研究，如反应恢复的可操作跑道测试中的模型；以及3)继续研究自我注射可卡因可能导致焦虑/厌恶的性质和神经生物学特性。在这项工作中使用的主要自我给药方法是一种独特的静脉药物强化的可操作性跑道测试。训练动物每天穿过一条直臂跑道，以获得党卫军进入球门区时提供的由静脉注射毒品(即可卡因、海洛因、速球、诺芬辛、可卡因)组成的奖励。在这种情况下，未服用药物的动物穿过跑道返回之前接受药物增强剂的地方的速度，为SS获得增强剂的动机提供了一个有效和高度可靠的指标。此外，由于动物每天只进行一次试验，因此产生的可操作数据没有药物增强剂本身产生的非特异性影响。由于动机状态(包括那些激发药物寻求行为的状态)部分是由内部激活或唤醒的存在来定义的，该项目已经开始使用小型植入式无线电遥测设备来提供生理数据(心率、呼吸、心电、核心温度……)。关于动物在行为测试期间的内部状态。这些行为和生理测量的结合将允许启动旨在调查中枢和交感神经系统在产生动机行为过程中的复杂关系的研究。实验计划是关于跑道上强化药物的IV和IC自我给药，以及在呈现预测药物的环境刺激时产生药物寻找行为“激活”的潜在机制。

DESCRIPTION (provided by applicant): The primary long-term goal of this project is to understand the neural mechanisms that contribute to the self-administration of opiate and stimulant drugs of abuse. Behavioral pharmacological methodologies will be applied to address three specific aims each of which builds upon and/or extends work conducted during the first fourteen years of this project. These are: 1) To dissociate the underlying motivational processes that serve to initiate drug-seeking behavior, from the reinforcing processes that are activated as a consequence of drug self-administration; 2) To continue and extend investigations of the mechanisms involved in the "relapse" of drug-abuse behavior as modeled in an operant runway test of response-reinstatement; and 3) To continue investigation of the nature and neurobiology of the putative anxiogenic/aversive properties of self-administered cocaine. The primary self-administration methodology employed in this work is a unique operant runway test of IV drug reinforcement. Animals are trained to traverse a straight arm runway once each day for a reward consisting of IV drug reinforcement (i.e., cocaine, heroin, speedball, nomefensine, cocaethylene) delivered upon the Ss' entry into the goal box. In this context, the speed with which the undrugged animal traverses the runway to return to a place where it had previously received the drug reinforcer, provides a valid and highly reliable index of the Ss' motivation to obtain the reinforcer. In addition, because the animals are tested on a single trial per day, the resulting operant data are devoid of nonspecific effects produced by the drug reinforcers themselves. Since motivated states (including those activate drug-seeking behavior) are defined, in part, by the presence of internal activation or arousal, the project has begun the use of small implanted radio-telemetric devices that provide physiological data (heart rate, respiration, ECG, core temperature...) about the internal state of the animal during behavioral testing. The combination of these behavioral and physiological measures will permit the initiation of studies intended to investigate the complex relationship between central and sympathetic nervous systems in the production of motivated behavior. Experiments are planned on the IV and IC self-administration of reinforcing drugs in the runway, on the underlying mechanisms that produce the "activation" of drug-seeking behavior upon presentation of drug-predictive environmental stimuli.