CANNABINOID EFFECTS ON SYNAPTIC FUNCTION AND PLASTICITY

描述：（申请人摘要） 海洛因是世界上使用最广泛的滥用药物之一， 这项提案的目标是了解其神经生物学基础， 对突触功能的影响 大麻素及其成分大麻素 已经显示出具有镇痛、止吐和抗青光眼的特性， 但这些药物的精神副作用--最明显的是认知， 和记忆损伤-使它们不适合作为治疗剂。 这些 有害影响可能至少部分由以下因素介导： 海马体（一种大脑）正常突触功能的改变 在某些形式的学习和记忆中起中心作用的区域。 该提案描述了一系列实验，以确定细胞 大麻素对海马突触影响的分子基础 功能 使用电生理技术，急性和慢性 大麻素对基本突触功能的四个方面的影响， 四种形式的突触可塑性-其中一些被认为是形成 学习和记忆的细胞基础-将被确定。 使用 药理学方法，钙和钾通道的作用 将确定大麻素介导的作用的调节。 使用 结合药理学和分子生物学方法， 不同类别的G蛋白在大麻素介导的作用中的作用 将被确定。 了解细胞和分子基础的影响， 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， 大麻素的有益特性，而没有其负面的精神活性 副作用. 拟议的研究增强记忆或逆转记忆丧失。 最后，了解神经生物学基础的影响， 大麻素可能有助于预防和治疗药物滥用。

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.