Torstenson R, Hartvig P, Långström B, Bastami S, Antoni G, Tedroff J
Uppsala University PET Centre, University Hospital, Uppsala University, Sweden.
Neuropharmacology. 1998 Aug;37(8):989-95. doi: 10.1016/s0028-3908(98)00085-9.
The effects of apomorphine on the striatal L-[11C]DOPA influx rate was examined in anaesthetized Rhesus monkeys using positron emission tomography (PET). In comparison with baseline conditions, the addition of a continuous infusion of apomorphine produced decreases in the striatal L-[11C]DOPA influx rate in all the monkeys examined. The effect of apomorphine infusion also showed a dose-dependent trend. In individual monkeys, the magnitude of the effect showed a baseline dopaminergic tone-dependency; that is, the effect of apomorphine was most pronounced in monkeys with high baseline influx rates, and in monkeys with lower baseline values apomorphine induced a weaker effect. Studies of radiolabeled tracer and radiolabeled metabolites formed in plasma confirmed that apomorphine infusion did not induce any change in the peripheral elimination or metabolite formation of L-[11C]DOPA. The decreased striatal L-[11C]DOPA influx rate induced by apomorphine was interpreted as an agonist effect on dopamine autoreceptors regulating the dopamine synthesis rate. The observation of a baseline dopaminergic tone-dependent effect is in agreement with earlier results showing this influence on the striatal influx rate as measured with the tracer L-[11C]DOPA. A priori, it can be established that L-[11C]DOPA and PET provide a method not only to study the structural integrity of the presynaptic dopaminergic system but also to study the homeostasis-regulating mechanisms of this neurotransmitter system in vivo. The ability to measure condition-dependent effects in individuals should be of great importance in determining specific pathophysiological mechanisms underlying degenerative and functional disorders affecting the dopaminergic system.
利用正电子发射断层扫描（PET）技术，在麻醉的恒河猴身上研究了阿扑吗啡对纹状体L-[11C]多巴流入率的影响。与基线条件相比，持续输注阿扑吗啡会使所有受试猴子的纹状体L-[11C]多巴流入率降低。阿扑吗啡输注的效果也呈现出剂量依赖性趋势。在个体猴子中，这种效果的大小呈现出基线多巴胺能张力依赖性；也就是说，阿扑吗啡的效果在基线流入率高的猴子中最为明显，而在基线值较低的猴子中，阿扑吗啡诱导的效果较弱。对血浆中放射性标记示踪剂和放射性标记代谢物的研究证实，阿扑吗啡输注并未引起L-[11C]多巴外周消除或代谢物形成的任何变化。阿扑吗啡诱导的纹状体L-[11C]多巴流入率降低被解释为对调节多巴胺合成速率的多巴胺自身受体的激动剂作用。基线多巴胺能张力依赖性效应的观察结果与早期结果一致，早期结果显示用示踪剂L-[11C]多巴测量时对纹状体流入率有这种影响。从先验角度可以确定，L-[11C]多巴和PET不仅提供了一种研究突触前多巴胺能系统结构完整性的方法，还提供了一种在体内研究该神经递质系统稳态调节机制的方法。在确定影响多巴胺能系统的退行性和功能性疾病潜在的特定病理生理机制方面，测量个体条件依赖性效应的能力应该非常重要。
