1. Synapse. 2010 Mar 17;64(8):617-623. [Epub ahead of print]

Influence of chronic bromocriptine and levodopa administration on cerebral type 1
cannabinoid receptor binding.

Casteels C, Vanbilloen B, Vercammen D, Bosier B, Lambert DM, Bormans G, Van Laere
K.

Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, 3000
Leuven, Belgium.

OBJECTIVES:: The endocannabinoid system is an important modulatory system in the 
brain. Complex interactions with brain dopaminergic circuits have been
demonstrated. The aim of this study was to investigate the in vivo effect of the 
commonly used antiparkinsonian drugs, levodopa (L-DOPA) and bromocriptine, on
type 1 cannabinoid (CB1) receptors, using the PET radioligand [(18)F]MK-9470.
EXPERIMENTAL APPROACH:: Seventeen female Wistar rats were studied at baseline and
after chronic exposure to either L-DOPA (6 mg/kg/day with 1.5 mg/kg/day
carbidopa; n = 6), bromocriptine (4 mg/kg/day; n = 5), or saline (n = 6).
[(18)F]MK-9470 binding was assessed in vivo using small animal PET imaging.
[(18)F]MK-9470 parametric images were generated, anatomically standardized to
Paxinos space and analyzed by voxel-based statistical parametric mapping (SPM2)
and a predefined volume-of-interest (VOI) approach. RESULTS:: In a 2 x 2 analysis
design (condition vs. treatment), no significant changes in absolute or relative 
[(18)F]MK-9470 binding were present upon chronic exposure to L-DOPA or
bromocriptine as compared to saline treatment. The post hoc comparison of chronic
scans to baseline within each treatment modality showed regional increases in
relative [(18)F]MK-9470 binding in the thalamus (peak average value +6.3%) and in
the sensorimotor cortex and hippocampus (peak average value +10.2%) after
bromocriptine exposure, while no changes were found for L-DOPA. CONCLUSION::
Chronic administration of L-DOPA and bromocriptine at the applied doses does not 
produce major cerebral changes in in vivo cannabinoid CB1 receptor binding of
[(18)F]MK-9470 in the rat brain. These results also suggest that similar chronic 
L-DOPA and bromocriptine usage is unlikely to interfere with human PET imaging in
healthy conditions using this radioligand. Synapse 2010. (c) 2010 Wiley-Liss,
Inc.

PMID: 20340169 [PubMed - as supplied by publisher]