Drugs of Abuse and Memory Span

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。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，用于研究啮齿动物记忆的程序通常仅限于研究在延迟间隔内对单一刺激或地点的保留。这项研究的目标是详细阐述最近开发的一项测试，评估啮齿动物在一次实验中记住越来越多气味的能力：嗅觉广度任务。这种方法为分析药物对记忆负荷的影响提供了新的可能性。Aim 1实验将确定滥用药物和其他被认为对嗅觉记忆有遗忘作用的选定化合物的急性影响，使用跨程序，包括苯二氮卓类药物（氯二氮吡酯，咪达唑仑），NMDA拮抗剂（二唑西平，氯胺酮），阿片类药物（吗啡），精神兴奋剂（哌甲酯，甲基苯丙胺，MDMA）和抗胆碱能致幻剂（东莨菪碱）。Aim 2实验将检查暴露于MDMA和甲基苯丙胺的神经毒性剂量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，本研究将为学生提供一个发展精神药理学和神经科学的技能和背景的理想机会。

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.