Mechanisms of Opiate and Stimulant Drug Reinforcement

描述（由申请人提供）：本项目的主要长期目标是了解有助于阿片类药物和兴奋剂滥用药物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，每个目标都建立在和/或扩展了本项目前14年期间进行的工作。这些措施是：（1）将引发药物寻求行为的潜在动机过程与药物自我给药后激活的强化过程分离开来;（2）继续并扩大对药物滥用行为“复发”机制的研究，如反应-恢复的操作性跑道测试;和3）继续研究自我给药可卡因的假定焦虑/厌恶性质的性质和神经生物学。这项工作中采用的主要自我管理方法是一个独特的操作跑道测试IV药物强化。训练动物每天一次穿过直臂跑道，以获得由IV药物强化组成的奖励（即，可卡因、海洛因、快球、诺美芬辛、古柯乙烯）。在这种情况下，未受伤害的动物穿过跑道返回到其先前接受药物注射器的地方的速度提供了S获得药物注射器的动机的有效且高度可靠的指标。此外，由于每天只对动物进行一次试验，因此所得的操作性数据缺乏药物本身产生的非特异性作用。由于动机状态（包括那些激活药物寻求行为的状态）在一定程度上是由内部激活或唤醒的存在来定义的，因此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，ECG，核心温度......）。关于动物在行为测试中的内部状态。这些行为和生理措施的结合，将允许旨在调查在动机行为的产生中枢和交感神经系统之间的复杂关系的研究开始。实验计划在IV和IC自我管理的加强药物在跑道上，对潜在的机制，产生“激活”的药物寻求行为后，介绍药物预测的环境刺激。

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.