In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

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• 作者：Kassiou ; Michael ; Eberl ; Stefan ; Meikle ; Steven R. ; Birrell ; Alex ; Constable ; Chris ; Fulham ; Michael J. ; et. al.
• 关键词：5-[¹²³I]-iodo-A-85380 ; (-)-Nicotine ; nAChR upregulation ; Quantitative dynamic SPECT
• 刊名：Nuclear Medicine and Biology
• 出版年：2001
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：February, 2001
• 卷：28
• 期：2
• 页码：165-175
• 文件大小：687 K

摘要

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[¹²³I]-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-[¹²³I]-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.