1. J Mol Neurosci. 2010 Oct;42(2):162-7. Epub 2010 Feb 25.

Influence of chronic nicotine administration on cerebral type 1 cannabinoid
receptor binding: an in vivo micro-PET study in the rat using [18F]MK-9470.

Gérard N, Ceccarini J, Bormans G, Vanbilloen B, Casteels C, Goffin K, Bosier B,
Lambert DM, Van Laere K.

Division of Nuclear Medicine, E901, Catholic University Leuven and University
Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
nathalie.gerard@uzleuven.be

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.


PMID: 20182818 [PubMed - in process]