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Influence of Chronic Nicotine Administration on Cerebral Type 1 Cannabinoid Receptor Binding: An In Vivo Micro-PET Study in the Rat Using [(18)F]MK-9470

By Nathalie Gérard, Jenny Ceccarini, Guy Bormans, Bert Vanbilloen, Cindy Casteels, Karolien Goffin, Barbara Bosier, Didier Lambert and Koen Van Laere

Abstract

Several lines of evidence suggest a functional interaction between central nicotinic and endocannabinoid systems. Furthermore, type 1 cannabinoid receptor (CB1R) antagonism is evaluated as antismoking therapy, and nicotine usage can be an important confound in positron emission tomography (PET) imaging studies of the CB1R. We evaluated CB1R binding in the rat brain using the PET radioligand [(18)F]MK-9470 after chronic administration of nicotine. Twelve female Wistar rats were scanned at baseline and after chronic administration of either nicotine (1 mg/kg; 2 weeks daily intraperitoneal (IP)) or saline as control. In vivo micro-PET images of CB1R binding were anatomically standardized and analyzed by voxel-based statistical parametric mapping and a predefined volume-of-interest approach. We did not observe changes in [(18)F]MK-9470 binding (p (height) < 0.001 level; uncorrected) on a group basis in either condition. Only at a less stringent threshold of p (height) < 0.005 (uncorrected) was a modest increase observed in tracer binding in the cerebellum for nicotine (peak voxel value + 6.8%, p (cluster) = 0.002 corrected). In conclusion, chronic IP administration of nicotine does not produce major cerebral changes in CB1R binding of [(18)F]MK-9470 in the rat. These results also suggest that chronic nicotine usage is unlikely to interfere with human PET imaging using this radioligand.status: publishe

Topics: Animals, Binding, Competitive, CHO Cells, Cerebral Cortex, Cricetinae, Cricetulus, Drug Administration Schedule, Female, Humans, Nicotine, Nicotinic Agonists, Positron-Emission Tomography, Protein Binding, Pyridines, Radioligand Assay, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1
Publisher: Birkhäuser Boston
Year: 2010
DOI identifier: 10.1007/s12031-010-9340-2
OAI identifier: oai:lirias.kuleuven.be:123456789/268704
Provided by: Lirias
Journal:

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