DRUG REINFORCEMENT MECHANISMS

药物强化机制

基本信息

批准号：
6332489
负责人：
JAMES E SMITH
金额：
$ 19.12万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-01-01 至 2000-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6332489
关键词：
6 hydroxydopamine autoradiography brain metabolism cocaine conditioning dopamine drug abuse experimental brain lesion heroin high performance liquid chromatography laboratory rat lenticular nucleus microdialysis neuropharmacology nucleus accumbens reinforcer tropanes

项目摘要

Cocaine abuse continues to be a significant public health problem. In spite of increased scientific investigation, the brain mechanisms responsible for compulsive cocaine use are still not clearly defined. The basic brain processes underlying compulsive cocaine use involve complex neuronal circuits and networks. Project five proposes continued investigation of these brain processes using a rat intravenous self- administration model. A recently completed turnover rate study in cocaine self-administering rats has suggested dopamine (DA), norepinephrine, serotonin, aspartate, glutamate and GABA releasing neurons in discrete brain regions to be important to the processes maintaining these behaviors. Experiments are proposed to use microdialysis and neurotoxin induced lesions to evaluate the involvement of and potential interrelationships between DA innervations of the ventral pallidum (VP) and nucleus accumbens (NA) in cocaine self-administration. In addition, the involvement of DA innervations of the NA and VP in the self- administration of cocaine-heroin combinations (speed ball) will be investigated using similar procedures. Another series of experiments will assess the effects of novel tropanes that attenuate cocaine self- administration on speed-ball administration to determine if these long acting and potent compounds also alter this intake. The overall goal of the proposed research for the next funding period is to further characterize the brain processes underlying compulsive use of cocaine and speed ball.

可卡因滥用仍然是一个重大的公共卫生问题。在尽管科学研究不断增加，但大脑机制造成可卡因成瘾的原因仍未明确界定。这强迫性使用可卡因的基本大脑过程涉及复杂的神经元回路和网络。项目五建议续使用大鼠静脉自体注射来研究这些大脑过程管理模式。最近完成的可卡因周转率研究自我给药大鼠建议使用多巴胺（DA）、去甲肾上腺素、血清素、天冬氨酸、谷氨酸和 GABA 释放神经元大脑区域对于维持这些过程很重要行为。实验建议使用微透析和神经毒素诱发病变以评估参与和潜在的腹侧苍白球 (VP) 的 DA 神经支配之间的相互关系和可卡因自我给药中的伏隔核（NA）。此外， NA 和 VP 的 DA 神经支配参与自我可卡因-海洛因组合（速度球）的管理将使用类似的程序进行调查。另一系列实验将评估新型托烷类药物减弱可卡因自我作用的效果快速球管理的管理以确定这些是否长作用和有效的化合物也会改变这种摄入量。总体目标为下一个资助期的拟议研究是为了进一步描述强迫性使用可卡因的大脑过程，以及速度球。