Kegeles L S, Zea-Ponce Y, Abi-Dargham A, Rodenhiser J, Wang T, Weiss R, Van Heertum R L, Mann J J, Laruelle M
Department of Psychiatry, Columbia University College of Physicians and Surgeons, and New York State Psychiatric Institute, New York 10032, USA.
Synapse. 1999 Mar 15;31(4):302-8. doi: 10.1002/(SICI)1098-2396(19990315)31:4<302::AID-SYN9>3.0.CO;2-A.
Binding competition between endogenous dopamine (DA) and the D2 receptor radiotracer [123I]IBZM allows measurement of the change in synaptic DA following amphetamine challenge with SPECT in the living human brain. Previous investigations using this technique in healthy subjects have shown that the magnitude of amphetamine effect on [123I]IBZM binding potential (BP) is small (range between 5 to 15% decrease), and that a large between-subject variability in this effect is observed. Therefore, it was unclear how much of the apparent between-subject variability was due to a low signal-to-noise ratio in the measurement, vs. true between-subject differences in the magnitude of the response. The goals of this investigation were to test the within-subject reproducibility and reliability of amphetamine-induced decrease in [123I]IBZM BP with a test/retest paradigm, and to establish the presence or absence of tolerance or sensitization to single administration ofi.v. amphetamine. Six healthy male subjects, never previously exposed to psychostimulants, twice underwent measurement of striatal amphetamine-induced DA release (between-measurement interval 16 +/- 10 days) using SPECT and the [123I]IBZM constant infusion technique. Results demonstrated an excellent within-subject reproducibility of amphetamine-induced DA release: amphetamine-induced decreases in [123I]IBZM BP were significant on each day, and had an intraclass correlation coefficient (ICC) of 0.89. Moreover, values from the second experiment were not significantly different from first experiment, suggesting the absence of either sensitization or tolerance to the effect of amphetamine on DA release in these experimental conditions. The subjective activation, as rated by the subjects on analog scales, was also highly reproducible. In conclusion, this scanning technique provides a reliable measurement of amphetamine-induced reduction of [123I]IBZM BP and enables detection of between-subject differences that appear stable over time.
内源性多巴胺（DA）与D2受体放射性示踪剂[123I]IBZM之间的结合竞争，使得在活体人脑中利用单光子发射计算机断层扫描（SPECT）测量苯丙胺激发后突触DA的变化成为可能。此前在健康受试者中使用该技术的研究表明，苯丙胺对[123I]IBZM结合潜能（BP）的影响幅度较小（降低幅度在5%至15%之间），且观察到这种影响在受试者之间存在较大差异。因此，尚不清楚受试者之间明显的差异中有多少是由于测量中的低信噪比所致，又有多少是由于受试者对反应幅度的真实个体差异。本研究的目的是采用重复测试范式，检验苯丙胺诱导的[123I]IBZM BP降低在受试者内的可重复性和可靠性，并确定对静脉注射苯丙胺单次给药是否存在耐受性或敏化作用。六名此前从未接触过精神兴奋剂的健康男性受试者，两次接受使用SPECT和[123I]IBZM持续输注技术测量纹状体苯丙胺诱导的DA释放（测量间隔为16±10天）。结果表明，苯丙胺诱导的DA释放在受试者内具有出色的可重复性：每天苯丙胺诱导的[123I]IBZM BP降低均具有显著性，组内相关系数（ICC）为0.89。此外，第二次实验的值与第一次实验的值无显著差异，表明在这些实验条件下，对苯丙胺对DA释放的作用不存在敏化或耐受现象。受试者用模拟量表评定的主观兴奋感也具有高度可重复性。总之，这种扫描技术能够可靠地测量苯丙胺诱导的[123I]IBZM BP降低，并能够检测出随时间推移似乎稳定的受试者间差异。
