Drugs of Abuse and Complex Behavior

描述（由申请人提供）：药物滥用与多种认知缺陷有关，包括学习和记忆的破坏。对于所谓的“俱乐部毒品”，例如亚甲二氧基甲基苯丙胺和甲基苯丙胺，这是一个特别令人关切的问题。描述这种损伤性质的一个主要困难是将药物对学习的影响与更普遍的表现下降分开。本研究的目标是利用大鼠模型确定几种俱乐部药物对学习的影响，该模型将重复获取技术的方法复杂性引入莫里斯游泳任务（莫里斯任务的二维模拟）和嗅觉辨别学习中的空间导航研究。在重复习得过程中，药物对已习得的问题的影响可以直接与对新问题的习得进行比较。实验1将确定MDMA、甲基苯丙胺和哌甲酯对大鼠空间导航习得（Morris游泳任务）的影响。实验二将使用触屏装置评估这三种药物对重复习得视觉辨别学习问题的影响。实验3将使用嗅觉辨别学习程序来研究这些药物。在所有三组研究中，将确定中等剂量药物的急性效应，并评估可能具有神经毒性的高剂量药物的残留效应。最后，同样的程序将用于评估NMDA拮抗剂苯环利定、二唑西平和LY235959的作用（实验4和5）。该项目的首要目标是继续开发和评估这些新方法作为评估药物对学习影响的工具的效用。

DESCRIPTION (provided by applicant): Drugs of abuse are associated with a variety of cognitive deficits including disruption of learning and memory. This is a particular concern with respect to the so-called "club drugs" such as methylenedioxymethamphetamine (MDMA) and methamphetamine. A major difficulty in characterizing the nature of such impairments is to separate the drug's effect on learning from more general performance decrements. The goal of the proposed research is determine the effects of several of the club drugs on learning using a rat model that brings the methodological sophistication of the repeated acquisitions technique to the study of spatial navigation in the Morris Swim Task, a two-dimensional analogue of the Morris Task, and olfactory discrimination learning. In the repeated acquisitions procedure, drug effects on a well-learned problem can be compared directly with acquisition of a new problem. Experiment 1 will determine the effects of the MDMA, methamphetamine, and methylphenidate on acquisition of spatial navigation (Morris Swim Task) in rats. Experiment 2 will evaluate the effects of the same three drugs using a touch-screen apparatus to study repeated acquisition of visual discrimination learning problems. Experiment 3 will study these drugs using an olfactory discrimination learning procedure. In all three sets of studies, the acute effects of moderate drug doses will be determined and the residual effects of potentially neurotoxic high doses will also be evaluated. Finally, the same procedures will be used to evaluate the effects of NMDA antagonists phencyclidine, dizocilpine and LY235959 (Experiments 4 & 5). An overarching goal of the project is to continue to develop and evaluate the utility of these new methodologies as tools in the assessment of drug effects on learning.