Laruelle M, Abi-Dargham A, van Dyck C H, Rosenblatt W, Zea-Ponce Y, Zoghbi S S, Baldwin R M, Charney D S, Hoffer P B, Kung H F
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
J Nucl Med. 1995 Jul;36(7):1182-90.
This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sulfate (d-amphetamine) challenge testing.
A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subjects first underwent a controlled experiment to demonstrate that stable levels of striatal and occipital activities could be maintained from 150 to 420 min during programmed infusion of the tracer. Next, seven subjects underwent the experiment with d-amphetamine. The experimental conditions were identical except that 0.3 mg/kg amphetamine was injected intravenously at 240 min. The behavioral effects of d-amphetamine were measured by self-rating on the following analog scales: euphoria, alertness, restlessness and anxiety.
The d-amphetamine injection induced a 15% +/- 4% (mean +/- s.d.) decrease in D2 receptor availability, measured as the specific-to-nonspecific equilibrium partition coefficient (V3"). The d-amphetamine injection induced marked increase in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availability measured with SPECT. In contrast, the anxiety response was milder and not correlated with the decrease in D2 availability.
These studies demonstrate the feasibility of using [123I]IBZM programmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correlates of emotions.
本研究评估了在硫酸右苯丙胺（d - 苯丙胺）激发试验后，使用单光子发射计算机断层扫描（SPECT）对人纹状体内突触多巴胺释放进行成像的可行性。
采用D2受体放射性示踪剂[123I]碘苄胺（[123I]IBZM）的静脉推注加持续输注给药方案，以获得稳定基线，用于可靠定量d - 苯丙胺的效应。8名健康受试者首先进行了一项对照实验，以证明在示踪剂的程序化输注过程中，纹状体和枕叶活动的稳定水平可在150至420分钟内维持。接下来，7名受试者进行了d - 苯丙胺实验。实验条件相同，只是在240分钟时静脉注射0.3mg/kg苯丙胺。通过以下模拟量表的自评来测量d - 苯丙胺的行为效应：欣快感、警觉性、烦躁不安和焦虑。
d - 苯丙胺注射导致D2受体可用性降低15%±4%（平均值±标准差），以特异性与非特异性平衡分配系数（V3”）衡量。d - 苯丙胺注射导致欣快感、警觉性和烦躁不安评分显著增加。这些行为反应的强度与用SPECT测量的D2可用性降低相关。相比之下，焦虑反应较轻微，且与D2可用性降低无关。
这些研究证明了使用[123I]IBZM程序化输注和SPECT成像来测量d - 苯丙胺激发后内源性多巴胺释放以及研究情绪的脑神经化学相关性的可行性。
