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

• Published in: Nuclear medicine and biology Vol. 28; no. 2; pp. 165 - 175
• Main Authors: Kassiou, Michael, Eberl, Stefan, Meikle, Steven R, Birrell, Alex, Constable, Chris, Fulham, Michael J, Wong, Dean F, Musachio, John L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2001; Elsevier
• Subjects: (-)-Nicotine; 5-[ 123I]-iodo-A-85380; Animals; Azetidines - pharmacokinetics; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Cerebellum - metabolism; Frontal Lobe - metabolism; Investigative techniques, diagnostic techniques (general aspects); Iodine Radioisotopes - pharmacokinetics; Kinetics; Male; Medical sciences; nAChR upregulation; Nervous system; Nicotine - pharmacology; Papio; Pyridines - pharmacokinetics; Quantitative dynamic SPECT; Radioligand Assay; Radionuclide investigations; Radiopharmaceuticals - pharmacokinetics; Receptors, Nicotinic - analysis; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Thalamus - metabolism; Tomography, Emission-Computed, Single-Photon; Up-Regulation; (-)-Nicotine; nAChR upregulation; Quantitative dynamic SPECT; 5-[ 123I]-iodo-A-85380; Radionuclide study; Monkey; Central nervous system; Binding site; Photon; In vivo; Vertebrata; Mammalia; Animal; Primates; Nicotinic receptor; Quantitative analysis; Brain (vertebrata); Iodine; Emission tomography
• ISSN: 0969-8051; 1872-9614
• 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-[ 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.