DRUG REINFORCEMENT MECHANISMS

滥用可卡因仍然是一个重大的公共卫生问题。在 尽管科学研究越来越多， 对强迫性可卡因使用的责任仍然没有明确界定。的 可卡因强迫性使用的基本大脑过程涉及复杂的 神经元回路和网络。项目五提议续 研究这些大脑过程使用大鼠静脉自我- 管理模式最近完成的可卡因周转率研究 自我给药的大鼠已经表明多巴胺（DA），去甲肾上腺素， 5-羟色胺，天冬氨酸，谷氨酸和GABA释放神经元在离散 大脑区域对维持这些过程很重要， 行为。提出了利用微透析和神经毒素进行实验 诱发的病变，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丘脑核（NA）。此外，本发明还提供了一种方法， 参与DA神经支配的NA和VP在自我- 可卡因-海洛因组合（速度球）的管理将是 使用类似的程序进行调查。另一系列实验将 评估减弱可卡因自身的新型托烷的作用， 管理速度球管理，以确定这些长 作用和有效的化合物也改变这种摄入。的总目标 下一个资助期的拟议研究将进一步 描述强迫使用可卡因的大脑过程， 速度球。

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.