A STUDY OF STIMULANT INDUCED CONDITIONED DRUG EFFECTS

众所周知，药物可以作为无条件的刺激和 诱导自主神经系统反应的巴甫洛夫条件效应。更多 然而，最近已经表明，行为过程，如 享乐状态、运动激活、渴求和行为药物 药物滥用可通过以下途径影响敏感化/耐受性 巴甫洛夫的条件反射机制。因为巴甫洛夫条件反射是一种 原始的，非自愿的学习形式，这种领域的扩展 巴甫洛夫条件反射包括复杂的生化和行为 滥用药物可以激活的过程具有重要的意义 对了解和治疗药物滥用问题的影响。 虽然巴甫洛夫条件反射被广泛认为是一种重要的 药物滥用的因素，到目前为止，还没有系统地研究过 动物模型。此外，中介的神经机制 巴甫洛夫条件性药物的作用似乎与 调节药物诱导的效应，因此未知。这种药 然而，我们最近开发的条件化方法提供了 为此建立实验基础的独特机会 行为药理学中重要但不发达的领域。这个 本研究提案的总体目标是使用我们的新技术 开发动物行为方法学以确定关键变量 和巴甫洛夫药物调节的神经生物学机制 过程将药物效应与外部感受性刺激联系起来。身份识别 重要变量是由巴甫洛夫条件反射原理和 包括药物剂量(即无条件刺激强度)、消退 以及自发康复。一系列研究将系统地 用选定的滥用药物来操纵这些变量。最初， 将对可卡因进行调查，随后将进行分析 扩展到包括咖啡因和吗啡。第二系列研究 以我们和其他人最近的观察为指导，这些观察结果表明 几个神经生物系统(例如，NMDA和阿片受体， 皮质酮和内侧前额叶皮质) 可卡因调理和/或敏化过程。这一系列 实验将提供关键信息来鉴定 可卡因条件作用的神经机制。另外， 由于可卡因的操纵涉及重复治疗，因此有可能 可卡因在大脑中的区域分布将发生变化 检查过了。总之，拟议的研究将发展一个广泛的 巴甫洛夫条件反射之间关系的经验基础 和滥用药物可以更好地理解和随后应用于 改进药物滥用治疗的治疗方式。

It is well-established that drugs can act as unconditioned stimuli and induce Pavlovian conditioned effects on autonomic system responses. More recently, however, it has been shown that behavioral processes such as hedonic states, motoric activation, craving and behavioral drug sensitization/tolerance can be impacted by drugs of abuse through Pavlovian conditioning mechanisms. Since Pavlovian conditioning is a primitive, involuntary form of learning this expansion of the domain of Pavlovian conditioning to include complex biochemical and behavioral processes which can be activated by drugs of abuse has important implications for the understanding and treatment of drug abuse problems. While Pavlovian conditioning is widely acknowledged to be an important factor in drug abuse, to date, it has not been systematically studied in animal models. In addition, the neural mechanisms which mediate Pavlovian conditioned drug effects appear to be separate from those which mediate the drug induced effects and are therefore unknown. The drug conditioning methodology we have recently developed, however, provides a unique opportunity to establish an experimental foundation for this important but underdeveloped area within behavioral pharmacology. The overall objective of the present research proposal is to use our newly developed animal behavior methodology to identify the critical variables and neurobiological mechanisms by which Pavlovian drug conditioning processes link drug effects to exteroceptive stimuli. The identification of important variables is guided by Pavlovian conditioning principles and incudes drug dose (i.e., Unconditioned Stimulus intensity), extinction and spontaneous recovery. One series of studies will systematically manipulate these variables with selected drugs of abuse. Initially, cocaine will be investigated and subsequently the analysis will be extended to include caffeine and morphine. The second series of studies are guided by our and others very recent observations which implicate several neurobiological systems (e.g., NMDA and opioid receptors, corticosterone and the medial prefrontal cortex) in the mediation of cocaine conditioning and/or sensitization processes. This series of experiments will provide critical information for the identification of neural mechanisms which underlie cocaine conditioning. Additionally, since the cocaine manipulations involve repeated treatments, possible changes in the regional distribution of cocaine in brain will be examined. Altogether, the proposed research will develop a broad empirical base upon which the relationship between Pavlovian conditioning and drugs of abuse can be better understood and subsequently applied to the improvement of treatment modalities for drug abuse therapy.