Exogenous/endogenous cannabinoids--Chemistry & behavior

描述：(申请人提供) 这项建议是对ISA(K02)的请求，它将加强我的研究 职业发展和扩展正在进行的关于大麻类和 相关化合物。我们在理解这一问题上的最新进展 大麻素作用的神经化学/生理学基础令人兴奋 继续努力进一步界定该机制的背景材料 拟大麻制剂的作用。拟议研究的总体目的 是比较主观效果的结构-活性关系 Delta-9-四氢大麻酚(Delta-9-THC)和其他具有 内源性大麻素受体配体的类似物[(R)-甲烷胺] 阿南达胺。化学结构和药物作用之间的SAR揭示了 对给定的药物效应或药物作用的结构要求。尽管有些人 研究表明，Delta-9-THC和双胺以及(R)-双胺 拥有许多相似的属性，一对一的关系 演示了。来自我们自己和其他实验室的研究表明， 合成大麻素和大麻仿制品的类THC特性非常高 取决于特定的结构配置。建议进行的研究 研究已知的拟大麻化合物的潜在立体选择性 关于(R)-甲烷胺。这些研究还侧重于确定有用的 通过有效地阻断精神活性物质来治疗大麻滥用， 模仿大麻的特性。本项目将利用毒品歧视 以大鼠为动物模型评估精神活性的程序 Delta-9-THC、(R)-甲烷和相关化合物的性质。药效 辨别是研究主观的最常用的范式， 药物在临床前精神药理学中的醉人作用。一份特别的 这项建议的特点是使用不同训练剂量的THC来 创造不同的功效需求。此外，食物保持了反应和 还将进行露天活动研究。通过提供重要的 内源性花生胺和外源β-9-THC的SAR信息，AS 作为潜在的大麻类拮抗剂，这些研究不仅将增加 对我们对大麻滥用和行为神经生物学的理解 依赖，但也可能导致开发有效的药理 治疗。

DESCRIPTION: (provided by applicant) This proposal is a request for an ISA (K02) which would enhance my research career development and extend ongoing research concerning cannabioids and related compounds. The recent advances in our understanding of the neurochemical/physiological basis of cannabinoid action provide exciting background material for continuing efforts to further delineate the mechanism of action of cannabimimetic agents. 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.