Drugs of Abuse and Complex Behavior

描述（由申请人提供）：药物滥用与各种认知缺陷相关，包括学习和记忆障碍。对于所谓的“俱乐部毒品”，如亚甲二氧基甲基安非他明和甲基安非他明，这是一个特别令人关切的问题。描述这种损伤的性质的一个主要困难是将药物对学习的影响与更普遍的性能下降分开。拟议的研究的目标是确定几个俱乐部的药物对学习的影响，使用大鼠模型，使重复采集技术的方法复杂的空间导航的研究中的莫里斯游泳任务，二维模拟的莫里斯任务，和嗅觉辨别学习。在重复获取过程中，药物对一个已学得很好的问题的影响可以直接与获取一个新问题进行比较。 实验1将确定MDMA、甲基苯丙胺和哌醋甲酯对大鼠空间导航（Morris游泳任务）获得的影响。 实验二采用触摸屏装置研究重复获得的视觉辨别学习问题，评价相同的三种药物的效果。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，将确定中等药物剂量的急性效应，并评价潜在神经毒性高剂量的残留效应。最后，将使用相同的程序来评估NMDA拮抗剂苯环己哌啶、地佐环平和LY 235959的作用（实验4和5）。 该项目的首要目标是继续开发和评价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.