COCAINE & MONOAMINERGIC SYSTEMS--IN VITRO STUDIES

与可卡因滥用有关的问题是多方面的，复杂的， 不太了解。 需要对可卡因滥用的所有方面进行研究， 包括神经生物学、行为学、临床、心理学和 社会性的 拟议研究的长期目标是更好地 了解可卡因的神经生物学，以便取得进展 在发展阶段。 然而，从迄今为止的研究来看， 可卡因的基本神经生物学必须在突触 水平 尽管迄今为止的证据表明， 单胺能系统在神经生物学中起着重要的作用， 可卡因，了解膜的潜在机制， 分子水平是稀疏的。 这项研究的更直接的目标是确定 可卡因改变单胺能神经元突触功能的机制 神经递质多巴胺去甲肾上腺素5羟色胺 这些机制将在 大鼠的突触体。 在没有可卡因的情况下， 与可卡因在培养中存在的实验相比， 解决方案 可卡因的浓度将在10-7和10-5之间变化 臼齿 具体目的是回答以下问题：（1）什么是 可卡因改变递质摄取的机制 (a)可卡因 影响发射器摄取的能量来源，或者通过改变 NA在运输中的作用或通过改变膜电位（EM）？ (2)是 可卡因对动力学常数的影响与产生的动力学常数相同 通过改变EM？(3)可卡因是通过什么机制 外源性递质释放 (4)可卡因的体外效应 不同于单次可卡因注射或连续三周每天注射 其他研究中会研究什么 实现拟议研究的具体目标将大大 扩大我们对可卡因影响这些机制的了解， 神经递质系统

The problems associated with cocaine abuse are multiple, complicated, and poorly understood. Studies of all aspects of cocaine abuse are needed, including neurobiological, behavioral, clinical, psychological, and societal. The long term objective of the proposed research is a better understanding of the neurobiology of cocaine so that progress may be made in the developmental stage. However, it seems clear from studies thus far that the basic neurobiology of cocaine must be understood at the synaptic level. Although the weight of the evidence thus far indicates that monoaminergic systems play an important role in the neurobiology of cocaine, knowledge of the underlying mechanisms at the membrane and molecular levels is sparse. The more immediate objective of this research is to determine the mechanisms by which cocaine alters synaptic function of the monoaminergic neurotransmitters, DA, NE, an 5-HT. These mechanisms will be studied in synaptosomes from the rat. Experiments in the absence of cocaine will be compared to experiments in which cocaine is present in incubation solutions. Concentration of cocaine will be varied between 10-7 and 10-5 molar. The specific aims are to answer the following questions: (1) What is the mechanism by which cocaine alters transmitter uptake? (a) Does cocaine affect the energy source for transmitter uptake, either by altering the role of NA in transport or by altering membrane potential (EM)? (2) Are the effects of cocaine on the kinetic constants the same as that produced by alteration in EM? (3) What is the mechanism by which cocaine alters exogenous transmitter release? (4) How do the in vitro effects of cocaine differ from single cocaine injections or daily injection for three weeks which will be examined in other studies? Accomplishment of the specific aims of the proposed research will greatly expand our knowledge of the mechanism of cocaine's effects on these neurotransmitter systems.