SPECT AND MICRODIALYSIS MEASUREMENT OF COCAINE ABUSE

当前应用程序的目标是开发或应用方法 用单光子发射（SPECT）研究多巴胺能系统 计算机断层扫描）和微透析，以评估神经化学 慢性可卡因引起的大脑变化 局 在上一个融资周期，我们成功地 实施SPECT方法（首先在猴子中，然后在人类中），以定量 多巴胺D2受体和多巴胺转运蛋白;将联合收割机i. v. 安非他明，用D2受体成像作为间接测量的挑战 突触多巴胺水平;以及将联合收割机微透析与SPECT成像相结合 以提供细胞外多巴胺水平的直接测量。 最近有两项PET研究表明，D2 非脱毒男性可卡因滥用者与健康男性相比， 使用[18F] N-甲基螺哌利多的雄性对照（Escherow等人，1990年至 1993年）。 D2受体的这些变化可能受到以下因素的混淆： 可卡因成瘾者的异常脑血流 我们建议比较 在活跃的可卡因滥用者和健康对照中的D2受体水平， 不受血流变化影响的平衡方法 （具体目标#1）。 此外，D2受体成像将结合 通过对多巴胺转运蛋白的持续研究， 可卡因依赖中多巴胺能传递的突触后测量。 由于年龄和性别可能对D2受体有重要影响，因此， 将研究男性和女性的数量，可卡因成瘾者和 对照组将在年龄上单独匹配。 此外，我们将 测量急性与急性期D2受体的潜在变化。 持续戒毒（具体目标#2）。 在动物研究中，我们将使用D2受体的SPECT成像， 在通过AMPT（α-甲基-对-酪氨酸）消耗DA后， 利血平检查D2受体占用诱导的基础水平的 内源性DA（目标#3）。 此外，我们亦会研究 SPECT受体成像和微透析测量 慢性安非他明给药诱导的致敏作用（目的#4）。 的 动物研究的设计是这样的，如果它们产生了阳性反应， 结果，我们将收集关键数据，以扩展这些范例， 研究滥用可卡因的人类受试者

The goals of the current application are to either develop or apply methods to study the dopaminergic system with SPECT (single photon emission computed tomography) and microdialysis to assess the neurochemical alterations in the brain which are induced by chronic cocaine administration. During the previous funding cycle, we successfully implemented SPECT methods (first in monkeys and then in humans) to quantify dopamine D2 receptors and dopamine transporters; to combine i.v. amphetamine,challenge with D2 receptor imaging as an indirect measure of synaptic dopamine levels; and to combine microdialysis with SPECT imaging to provide direct measurements of extracellular dopamine levels. Two PET studies have recently demonstrated significant reductions in D2 receptors in non-detoxified male cocaine abusers as compared to healthy male controls using [18F]N-methylspiroperidol (Volkow et al., 1990 and 1993). These alterations in D2 receptors could have been confounded by abnormal cerebral blood flow in the cocaine addicts. We propose to compare levels of D2 receptors in active cocaine abusers and healthy controls using an equilibrium method which is not influenced by alterations of blood flow (Specific Aim #1). In addition, the D2 receptor imaging will be combined with on- going studies of the dopamine transporter to provide both pre- and postsynaptic measures of dopaminergic transmission in cocaine dependence. Since age and gender may have important effects on D2 receptors, equal numbers of males and females will be studied and cocaine addicts and controls will be individually matched for age. In addition, we will measure potential changes in D2 receptors during states of acute vs. sustained drug abstinence (Specific Aim #2). In the animal studies, we will use SPECT imaging of the D2 receptor before and after depletion of DA by AMPT (alpha-methyl-para-tyrosine) and reserpine to examine D2 receptor occupancy induced by basal levels of endogenous DA (Aim #3). In addition, we will examine the ability of the ability of both SPECT receptor imaging and microdialysis to measure sensitization induced by chronic amphetamine administration (Aim #4). The animal studies have been designed so that, if they generate positive results, we will have gathered critical data to extend these paradigms to study human subjects who abuse cocaine.