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In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy
Author(s) -
Yakushev Igor Y.,
Dupont Erwan,
Buchholz HansGeorg,
Tillmanns Julia,
Debus Fabian,
Cumming Paul,
Heimann Axel,
Fellgiebel Andreas,
Luhmann Heiko J.,
Landvogt Christian,
Werhahn Konrad J.,
Schreckenberger Mathias,
Potschka Heidrun,
Bartenstein Peter
Publication year - 2010
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2009.02272.x
Subject(s) - dopamine , pilocarpine , dopaminergic , putamen , dopamine receptor , striatum , epilepsy , dopamine receptor d2 , neuroscience , medicine , endocrinology , biology
Summary Purpose: Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy. Methods: Six pilocarpine‐treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [ 18 F]‐fallypride, a high‐affinity dopamine D 2/3 receptor ligand. Parametric images of [ 18 F]‐fallypride specific binding were calculated using a reference tissue method, and the two groups were contrasted by whole‐brain voxel‐based analysis implemented in statistical parametric mapping (SPM5). Results: Dopamine D 2/3 receptor availability was 27% lower in the bilateral anterior caudate‐putamen of pilocarpine‐treated rats as compared to controls (p < 0.05), but binding was unaffected in other striatal or extrastriatal regions. Conclusions: The finding of substantially reduced availability of dopamine D 2/3 receptors in the anterior caudate‐putamen of rats during the chronic phase of the pilocarpine model is in agreement with results of invasive (microinjection, microdialysis) animal studies that have revealed increased dopamine tonus and a D 2/3 receptor–mediated anticonvulsant action of dopamine in the anterior segment of the rat striatum. The present PET approach could be prospectively applied for monitoring dopamine receptor changes longitudinally, that is, at different phases of the epileptogenic process, and opens perspectives for testing dopaminergic agents as potential antiepileptogenic drugs.