PET STUDIES OF BRAIN DOPAMINE IN COCAINE ABUSERS

我们建议使用正电子发射断层扫描(PET)来评估 可卡因滥用者额叶代谢增加与降低有关 突触前DNA神经元的功能。我们假设减少了 PDN的功能扰乱了额区的活动 大脑皮层DA系统和这些额叶区域的破坏是 导致失控和驱使 强制给上瘾的人注射可卡因。我们会 通过监测对PDN的反应来评估PDN的功能 药理学挑战将是哌酸甲酯(MP)，这是一种药物，像 可卡因，通过抑制DA转运蛋白而增加DA。我们会 用正电子发射计算机断层扫描间接测定多巴胺释放监测甲基强的松龙对机体的影响 11C-拉克洛必利结合。由于内源性DA与11C-拉氯普利竞争 与DA受体的结合；Inoue et，这一策略将允许我们 测量继发于MP的DA浓度的相对变化。其有效性 这一过程的可靠性已经在最近的几个月中得到了讨论 出版物。为了评估DA变化对大脑功能的影响，我们 还将测量MP对大脑局部葡萄糖代谢的影响 2-脱氧-2[18F]氟-D-葡萄糖(18FDG)。信度和效度 FDG测试/重新测试的设计已在其他地方描述。为了这些 研究我们将招募男性和女性可卡因滥用者(n=20)和 匹配的男性和女性对照组(n=20)。

We propose to use Positron Emission Tomography (PET) to evaluate if creased frontal metabolism in cocaine abusers is related to decreased function of presynaptic DNA neurons (PDN). We hypothesize that decreased function of PDN disrupts the activity of frontal regions modulated by the mesocortical DA system and that disruption of these frontal regions is one of the mechanisms leading to the loss of control and the drive to compulsively administer cocaine in the addicted individual. We will evaluate the function of PDN by monitoring its response to a pharmacological challenge will be methylphenidate (MP), a drug which, like cocaine, increases DA via inhibition of the DA transporter. We will measure DA release indirectly using PET to monitor the effects of MP on 11C-raclopride binding. Since endogenous DA competes with 11C-raclopride binding for the DA receptor; Inoue et, this strategy will allow us to measure relative changes in DA concentration secondary to MP. The validity and reliability of this procedure has been discussed in several recent publications. To evaluate the effects of DA changes on brain function, we will also measure the effects of MP on regional brain glucose metabolism with 2-deoxy-2[18F]fluoro-D-glucose (18FDG). The reliability and validity of the FDG test/retest design has been described elsewhere. For these studies we will recruit male and female cocaine abusers (n=20 each) and matched male and female controls (n=20 each).