在人类大脑中，[11C]雷氯必利对哌醋甲酯反应时内源性多巴胺竞争重复测量的可重复性。
Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate.
作者信息
Wang G J, Volkow N D, Fowler J S, Logan J, Pappas N R, Wong C T, Hitzemann R J, Netusil N
机构信息
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
出版信息
J Nucl Med. 1999 Aug;40(8):1285-91.
UNLABELLED
The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures.
METHODS
Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility.
RESULTS
Measures of plasma to brain transfer constant (K1), striatal distribution volume (DVstr) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77+/-0.44; E2: 2.97+/-0.44). MP administration did not change K1, but it significantly decreased DVstr (E1: -25.9%+/-8.7%, P < or = 0.0002; E2: -20.7%+/-11.7%, P < or = 0.007) and Bmax/Kd (E1: -18.4%+/-8.7%, P < or = 0.002; E2: -13.4%+/-9.2%, P < or = 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate (E1: +64%+/-43%, P < or = 0.002; E2: +69%+/-33%, P < or = 0.001), systolic pressure (E1: +37%+/-19%, P < or = 0.0006; E2: +29%+/-15%, P < or = 0.0009), self reports for drug effects (0: nothing to 10: extreme) of "rush" (E1: +8+/-3, P < or = 0.0004; E2: +6+/-4, P < or = 0.01) and "high" (E1: +8+/-3, P < or = 0.0001, E2: +8+/-3, P < or = 0.0003), anxiety (E1: +5+/-4, P < or = 0.02; E2: +4+/-4, P = 0.1) and restlessness (E1: +4+/-4, P < or = 0.04; E2: +4+/-5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2.
CONCLUSION
MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.
未标注
测量突触多巴胺（DA）浓度对精神兴奋药物哌甲酯（MP）的反应变化，已被用作DA系统反应性的指标。本研究的目的是评估这些测量的可重复性。
方法
7名健康受试者在同一天接受两次PET和[11C]雷氯必利扫描：分别在服用安慰剂或哌甲酯（0.5mg/kg）后7分钟。同时，我们还测量了对安慰剂和哌甲酯的生理和行为反应。1-2周后重复相同程序以评估重测的可重复性。
结果
对于安慰剂条件，血浆到脑的转运常数（K1）、纹状体分布容积（DVstr）和DA D2受体可用性（Bmax/Kd）的测量在首次（E1）和第二次（E2）评估中相似（Bmax/Kd，E1：2.77±0.44；E2：2.97±0.44）。服用MP未改变K1，但显著降低了DVstr（E1：-25.9%±8.7%，P≤0.0002；E2：-20.7%±11.7%，P≤0.007）和Bmax/Kd（E1：-18.4%±8.7%，P≤0.002；E2：-13.4%±9.2%，P≤0.008），且这些变化的幅度虽然E2时较低，但差异无统计学意义。MP增加了脉搏率（E1：+64%±43%，P≤0.002；E2：+69%±33%，P≤0.001）、收缩压（E1：+37%±19%，P≤0.0006；E2：+29%±15%，P≤0.0009）、自我报告的药物效应（0：无至10：极度）“冲动”（E1：+8±3，P≤0.0004；E2：+6±4，P≤0.01）和“兴奋”（E1：+8±3，P≤0.0001，E2：+8±3，P≤0.0003）、焦虑（E1：+5±4，P≤0.02；E2：+4±4，P = 0.1）和坐立不安（E1：+4±4，P≤0.04；E2：+4±5，P = 0.1）。E1和E2之间心血管和行为效应的幅度无差异。
结论
重复给药时，MP诱导的纹状体DV和Bmax/Kd变化以及行为和心血管效应具有可重复性。
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