NEURAL MECHANISMS OF CANNABINOID ACTIVITY

尽管自然产生的和合成的大麻素的影响 已经很好地描述过了，它们的作用机制才刚刚开始 为人所知。最近的突破性进展表明， 大麻素受体及其受体mRNA在中枢神经系统的分布 强烈提示大麻素神经元通路的存在。这个 本项目提出的研究目标是：1)确定 特定的大脑区域，它介导了行为的影响 大麻素，以及2)大麻素神经元通路的特征。这些 拟议的研究将集中在海马体和基底节上，因为， 除了含有高浓度的大麻素受体和 大麻素受体mRNA，它们介导了许多相关的行为 有大麻素活性。将评估的行为指标 是伤害性感觉，眩晕，短期记忆，自发活动， 体温过低和旋转行为。使用一种药理学方法， 这将包括剂量反应和SAR研究，影响 将对特定大脑部位的大麻类物质进行检查。在一个单独的 一系列的研究，神经通路的特征将是 含有高密度脂蛋白的特定脑结构的选择性病变 大麻素受体或大麻素受体mRNA的浓度。 放射自显影和原位杂交组织化学方法 然后用来评估受体数量和表达的变化 大麻素受体基因的表达。这项研究的结果 将是阐明神经的重要的第一步 大麻素活性物质。

Though the effects of naturally occurring and synthetic cannabinoids have been well described, their mechanisms of action are just beginning to become known. Recent breakthrough demonstrating differences between the distribution of cannabinoid receptors and the receptor mRNA in the CNS strongly suggest the existence of cannabinoid neuronal pathways. The objectives of the research proposed in this project are to: 1) identify specific brain region which mediate the behavioral effects of the cannabinoids, and 2) characterize cannabinoid neuronal pathways. These proposed studies will focus on the hippocampus and basal ganglia because, in addition containing high concentrations of cannabinoid receptors and cannabinoid receptor mRNA, they mediate many of the behaviors associated with cannabinoid activity. The behavioral indices which will be assessed are the nociception, catalepsy, short-term memory, spontaneous activity, hypothermia, and rotational behavior. Using a pharmacological approach, which will include dose-response and SAR studies, the effects of cannabinoids in specific brain sites will be examined. In a separate series of studies, the neuronal pathways will be characterized by selective lesions of specific brain structures containing high concentrations of cannabinoid receptors or cannabinoid receptors mRNA. The methods of autoradiography and in situ hybridization histochemistry will then be used to assess changes in receptor number and expression of cannabinoid receptor mRNA, respectively. The results of this research will be an important first step in the elucidation of the neural substances of cannabinoid activity.