DRUG REINFORCEMENT MECHANISMS

可卡因滥用仍然是一个严重的公共卫生问题。在……里面 尽管科学研究增加了，但大脑机制 对强制使用可卡因负有责任的人仍然没有明确的定义。这个 强迫性使用可卡因背后的基本大脑过程涉及复杂的 神经元电路和网络。项目五提议继续 大鼠静脉注射自体脑的上述脑过程的研究 管理模式。最近完成的可卡因周转率研究 自我给药的大鼠建议多巴胺(DA)，去甲肾上腺素， 离散型5-羟色胺、天冬氨酸、谷氨酸和GABA释放神经元 大脑区域对维持这些功能的过程很重要 行为。建议使用微透析和神经毒素进行实验 诱导损伤评估受累程度和潜在性 苍白球腹侧区(Vp)DA神经分布的相互关系 和伏核(NA)在可卡因自身给药中。此外, NA和VP的DA神经支配在自我调节中的作用 可卡因-海洛因组合(速球)的管理将是 使用类似程序进行调查。另一系列实验将 评估新型硫代巴比妥类药物对可卡因自身的影响 关于速球管理的管理，以确定这些长时间 活性和强效化合物也会改变这种摄入量。的总目标是 下一个资助期的拟议研究将进一步 描述强迫性使用可卡因的大脑过程和 快速球。

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.