Kassiou M, Eberl S, Meikle S R, Birrell A, Constable C, Fulham M J, Wong D F, Musachio J L
Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia.
Nucl Med Biol. 2001 Feb;28(2):165-75. doi: 10.1016/s0969-8051(00)00206-7.
To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V(d) ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V(d) was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V(d) or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment.
为了量化体内神经元烟碱型乙酰胆碱受体（nAChR）结合的变化，在狒狒接受（-）-尼古丁或生理盐水对照的慢性治疗前后，用5-[(123)I]-碘-A-85380进行了定量动态单光子发射计算机断层扫描（SPECT）研究。以2.0mg/kg/24h的剂量输注（-）-尼古丁14天，导致血浆（-）-尼古丁水平达到27.3ng/mL。这与普通人类吸烟者（每天20支香烟）的水平相当。在狒狒脑中，5-[(123)I]-碘-A-85380的区域分布与已知的nAChR密度一致（丘脑>额叶皮质>小脑）。nAChR结合的变化通过三室模型拟合得出的分布容积（V(d)）和结合潜能（BP）进行估计。在（-）-尼古丁治疗的动物中，（-）-尼古丁治疗停止7天后，丘脑（52%）和小脑（50%）的V(d)显著增加，提示nAChRs上调。额叶皮质观察到的33%的增加未达到显著水平。丘脑中BP显著增加。在生理盐水对照动物中，在任何实验条件下V(d)或BP均未观察到变化。在这项初步研究中，我们首次证明了慢性（-）-尼古丁治疗后体内神经元nAChR结合上调。
