Drugs of Abuse and Memory Span

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。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限于研究单个刺激或位置在延迟间隔内的保留。这项研究的目标是详细阐述最近开发的一项测试，该测试评估了啮齿动物在单一实验会话中记住越来越多气味的能力：嗅觉广度任务。这一过程提供了新的潜力，分析药物的影响作为记忆负荷的函数。目标1实验将使用跨度程序确定滥用药物和其他被认为对嗅觉记忆具有遗忘作用的选定化合物的急性效应，包括苯二氮卓类（利、咪达唑仑）、NMDA拮抗剂（地佐西平、氯胺酮）、阿片类（吗啡）、精神兴奋剂（哌醋甲酯、甲基苯丙胺、MDMA）和抗胆碱能致幻剂（东莨菪碱）。目标2实验将检查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留影响，这些剂量与人类和一些动物模型中的遗忘效应有关。该项目的首要目标是开发和评估这种新方法，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理想的机会，发展技能和背景的精神药理学和神经科学。 公共卫生相关性：滥用药物可能会导致认知能力受损，本项目将开发一种新的动物模型，以确定和描述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.