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

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[I-123]-iodo-A- 85380 in baboons pre a nd 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 avera ge human smoker (20 cigarettes a day). In the baboon brain the regional dis tribution of 5-[I-123]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR bindi ng were estimated from the volume of distribution (V-d) and binding potenti al (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 upre gulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamu s. In the saline control animal no changes were observed in V-d or BP under any experimental conditions. In this preliminary study, we have demonstrat ed for the first time in vivo upregulation of neuronal nAChR binding follow ing chronic (-)-nicotine treatment. (C) 2001 Elsevier Science Inc. All righ ts reserved.