EXOGENOUS AND ENDOGENOUS CANNABINOIDS--A COMPARISON

拟议研究的总体目的是比较结构- δ-9主观效应的活动关系- 四氢大麻酚（δ-9-THC）和其他大麻模拟物， 内源性大麻素受体配体的类似物（R-甲酰胺） 花生四烯酸 化学结构和药物作用之间的SAR揭示了 特定药物作用或药物作用的结构要求。 尽管一些研究表明，δ-9-THC和大麻素以及 R-甲酰胺具有许多相似的性质，一对一 关系尚未得到证实。 我们自己和其他人的研究 实验室已经证明了合成的THC的类似性质 大麻素和拟大麻素高度依赖于特定的 结构配置。 拟议的研究调查了潜在的 已知大麻拟似化合物关于R-的立体选择性 甲烟酰胺 这些研究还侧重于确定有用的 药物治疗大麻滥用，有效地阻止 精神刺激类大麻物质 本项目将 利用大鼠作为动物模型的药物辨别程序， 评估δ-9-THC，R-甲酰胺， 和相关化合物。 毒品歧视是最常用的 研究药物的主观、致醉作用的范例， 临床前精神药理学 这项建议的一个特点是 使用不同训练剂量的THC以产生不同的功效 要求。 此外，食物保持响应和开放领域 并会进行活动研究。 通过提供重要的 内源性花生四烯酸和外源性δ-9- THC以及潜在的大麻模拟物拮抗剂，这些研究将 不仅加深了我们对行为神经生物学的理解， 大麻滥用和依赖，但也可能导致发展， 有效的药物治疗。

The overall purpose of the proposed studies is to compare the structure- activity relationships of the subjective effects of delta-9- tetrahydrocannabinol (delta-9-THC) and other cannabimimetics with an analog (R-methanandamide) of the endogenous cannabinoid receptor ligand anandamide. The SAR between chemical structure and drug action reveals the structural requirements for a given drug effect or drug action. Though some studies suggest that delta-9-THC and anandamide as well as R-methanandamide share many similar properties, a one-on-one relationship has not been demonstrated. Studies from our own and other laboratories have shown the THC-like properties of synthetic cannabinoids and cannabimimetics are highly dependent on particular structural configurations. The proposed studies investigate potential stereoselectivity of known cannabimimetic compounds with regard to R- methanandamide. These studies also focus on identifying useful pharmacotherapies for cannabis abuse by effectively blocking the psychoactive, cannabimimetic properties. The present project will utilize drug discrimination procedures with rats as an animal model for assessing the psychoactive properties of delta-9-THC, R-methanandamide, and related compounds. Drug discrimination is the most commonly used paradigm for studying the subjective, intoxicating effects of drugs in preclinical psychopharmacology. A special feature of this proposal is the use of different training doses of THC to create different efficacy demands. Additionally, food maintained responding and open-field activity studies will also be conducted. By providing important information on the SAR of endogenous anandamide and exogenous delta-9- THC, as well as potential cannabimimetic antagonists, these studies will not only add to our understanding of the behavioral neurobiology of cannabis abuse and dependence, but may also lead to the development of effective pharmacological treatments.