CANNABINOID EFFECTS ON SYNAPTIC FUNCTION AND PLASTICITY

大麻素对突触功能和可塑性的影响

• 批准号: 2882640
• 负责人: JANE M SULLIVAN
• 金额: $ 12.46万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882640
• 关键词: G protein; acute disease /disorder; calcium channel; cannabinoids; cellular pathology; chronic disease /disorder; cognition; depression; drug adverse effect; drug screening /evaluation; electrophysiology; hippocampus; laboratory rat; marijuana abuse; memory; molecular pathology; neural plasticity; neural transmission; neurobiology; neurons; neurotransmitter metabolism; pharmacokinetics; potassium channel; synapses; tissue /cell culture

DESCRIPTION: (Applicant's Abstract) Marijuana is one of the most widely used drugs of abuse in the world, and it is the goal of this proposal to understand the neurobiological basis for its effects on synaptic function. Marijuana and its constituent cannabinoids have been shown to have analgesic, antiemetic and antiglaucoma properties, but the psychoactive side effects of these drugs - most notably, cognition and memory impairments - make them undesirable as therapeutic agents. These detrimental effects are likely to be mediated, at least in part, by alteration of the normal synaptic functioning of the hippocampus, a brain region that plays a central role in certain forms of learning and memory. This proposal describes a series of experiments to determine the cellular and molecular basis for the effects of cannabinoids on hippocampal synaptic function. Using electrophysiological techniques, the acute and chronic effects of cannabinoids on four aspects of basic synaptic function, and on four forms of synaptic plasticity - some of which are believed to form the cellular basis for learning and memory - will be determined. Using a pharmacological approach, the role of calcium and potassium channel modulation in cannabinoid-mediated effects will be determined. Using a combination of pharmacological and molecular biological approaches, the roles of different classes of G-proteins in cannabinoid-mediated effects will be determined. Understanding the cellular and molecular basis for the effects of cannabinoids on cognition and memory is a necessary first step in the rational design of selective therapeutic agents that can replicate the beneficial properties of cannabinoids without their negative psychoactive side effects. The proposed studies enhance memory or reverse memory loss. Finally, understanding the neurobiological basis for the effects of cannabinoids may aid in drug abuse prevention and treatment.

描述：（申请人摘要） 大麻是世界上使用最广泛的滥用药物之一，它 该提案的目标是了解其神经生物学基础 对突触功能的影响。 大麻及其成分大麻素 已被证明具有镇痛、止吐和抗青光眼特性， 但这些药物的精神副作用 - 最明显的是认知能力 和记忆障碍 - 使它们不适合作为治疗剂。 这些 有害影响可能至少部分是由 海马体（大脑）正常突触功能的改变 在某些形式的学习和记忆中发挥核心作用的区域。 该提案描述了一系列实验来确定细胞 大麻素对海马突触影响的分子基础 功能。 利用电生理学技术，急性和慢性 大麻素对基本突触功能四个方面的影响，以及 突触可塑性的四种形式 - 其中一些被认为形成 学习和记忆的细胞基础 - 将被确定。 使用 药理途径、钙钾通道的作用 将确定大麻素介导效应的调节。 使用 药理学和分子生物学方法的结合， 不同类别的 G 蛋白在大麻素介导的效应中的作用 将被确定。 了解影响的细胞和分子基础 大麻素对认知和记忆的影响是必要的第一步 合理设计选择性治疗药物，可以复制 大麻素的有益特性，但没有负面的精神活性 副作用。 拟议的研究可以增强记忆或逆转记忆丧失。 最后，了解影响的神经生物学基础 大麻素可能有助于药物滥用的预防和治疗。