INVOLVEMENT OF THE SEPTAL NUCLEI IN THE ABUSE OF COCAINE

可卡因滥用及其相关毒性显然是一个主要的健康问题 今天在美国。 由于严重的 与可卡因使用有关的不良后果，迫切需要 开发可能阻止可卡因滥用的药物，和/或 防止其急性和慢性毒性。 以制订和 设计这样的药物，可卡因的细胞作用机制需要 测定 因此，本提案的目的是调查，在 细胞水平，可卡因改变化学物质的机制 神经递质和神经调质与中枢神经元的相互作用 与大脑奖励机制有关的基因 由此推论 目的是调查可卡因可能的机制，除此之外， 在这些相同的固有电活动之后， 神经元 先前研究可卡因的作用集中在多巴胺上， 系统 这项研究的结果显然表明， 多巴胺在可卡因使用引起的奖赏机制中的作用。 然而，在这方面， 多巴胺并不是唯一的调节剂， 生理和行为上的影响。 这项建议 将检查六种不同的神经递质/神经调质受体， 包括多巴胺，以阐明有助于 可卡因滥用的多重后遗症 选择隔核内的神经元进行研究是因为它们具有 已知在正常和异常的人类表达中起关键作用， 情绪和行为 细胞内电生理技术， 体外，将为我们提供方法，以提供新的见解， 可卡因的细胞作用机制。 从这些获得的知识 实验将提供必要的信息，用于打击 急性和慢性可卡因使用和毒性。

Cocaine abuse and its associated toxicity is clearly a major health problem today in the United States. Because of the significant incidence of severe adverse consequences associated with cocaine use there is a desperate need to develop drugs that can potentially deter the abuse of cocaine and/or protect against its acute and chronic toxicity. In order to develop and design such drugs, the cellular mechanisms of action of cocaine need to be determined. Thus, the goal of this proposal is to investigate, at the cellular level, the mechanisms by which cocaine alters the chemical interaction of neurotransmitters and neuromodulators with central neurons that have been implicated in brain reward mechanisms. A corollary of this goal is to investigate mechanisms by which cocaine may, in addition to that suggested above, after the inherent electrical activities of these same neurons. Prior research examining the action of cocaine has focused on the dopamine system. The results of that research implicate, clearly, an involvement of dopamine in the mechanism of reward resulting from cocaine use. However, dopamine is not the sole mediator responsible for the many and varied physiological and behavioral effects contributed to cocaine. This proposal will examine six different neurotransmitter/neuromodulator receptors, including dopamine, in order to clarify the mechanisms that contribute to the multiple sequelae of cocaine abuse. Neurons within the septal nuclei have been chosen to study because of their known pivotal involvement in the expression of normal and abnormal human emotions and behavior. Intracellular electrophysiological techniques, in vitro, will afford us the methodology to provide new insights into the cellular mechanisms of action of cocaine. Knowledge obtained from these experiments will provide essential information to use in the fight against acute and chronic cocaine use and toxicity.