Drugs of Abuse and Memory Span

描述(申请人提供)：滥用药物与各种认知缺陷有关，包括学习和记忆障碍。需要动物模型来更好地评估使用和滥用精神活性药物的认知风险。然而，可用于研究啮齿动物记忆的程序通常仅限于研究单一刺激或跨延迟间隔的位置的保留。这项拟议的研究的目标是详细说明最近开发的一项测试，该测试评估啮齿类动物在单一实验阶段记住越来越多气味的能力：嗅觉广度任务。这一过程为分析药物的影响作为记忆负荷的函数提供了新的可能性。目的1实验将采用SPAN程序确定滥用药物和其他被认为对嗅觉记忆有遗忘作用的化合物的急性效应，包括苯二氮卓类药物(氯氮卓酮、咪达唑仑)、NMDA拮抗剂(地佐西平、氯胺酮)、阿片类药物(吗啡)、精神刺激剂(哌甲酯、甲基苯丙胺、MDMA)和抗胆碱能迷幻剂(东莨菪碱)。Aim 2实验将检验暴露于神经毒性剂量的MDMA和甲基苯丙胺后对记忆广度的残余影响，这些剂量与人类和一些动物模型的遗忘效应有关。该项目的一个主要目标是开发和评估这种新的方法，作为评估药物对记忆影响的工具。最后，拟议的研究将为学生提供一个发展精神药理学和神经科学方面的技能和背景的理想机会。 公共卫生相关性：滥用药物可能导致认知缺陷，该项目将开发一种新的动物模型，以识别和表征滥用药物对记忆能力的急性和残留影响。

DESCRIPTION (provided by applicant): Drugs of abuse are associated with a variety of cognitive deficits including disruption of learning and memory. Animal models are needed to better assess the cognitive risks of use and abuse of psychoactive drugs. However, procedures available to study memory in rodents are generally limited to the study of retention of a single stimulus or place across a delay interval. The goal of the proposed research is to elaborate a recently developed test that assesses rodent's ability to remember an increasing number of odors within a single experimental session: the olfactory span task. This procedure offers the novel potential to analyze the effects of drugs as a function of memory load. Aim 1 experiments will determine the acute effects of drugs of abuse and other selected compounds that are thought to have amnestic effects on olfactory memory using the span procedure including benzodiazepines (chlordiazepoxide, midazolam), NMDA antagonists (dizocilpine, ketamine), opiates (morphine), psychostimulants (methylphenidate, methamphetamine, MDMA), and an anticholinergic hallucinogen (scopolamine). The Aim 2 experiments will examine residual effects on memory span after exposure to neurotoxic doses of MDMA and methamphetamine that have been associated with amnestic effects in humans and in some animal models. An overarching goal of the project is to develop and evaluate this new methodology as a tool in the assessment of the effects of drugs on memory. Finally, the proposed research will provide an ideal opportunity for students to develop skills and background in psychopharmacology and neuroscience. PUBLIC HEALTH RELEVANCE: Drugs of abuse may produce cognitive deficits and this project will develop a new animal model to identify and characterize acute and residual effects of abused drugs on memory capacity.