In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy.
OBJECTIVE
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.
Yakushev
Igor Y
IY
Department of Nuclear Medicine, University of Mainz, Mainz, Germany. igor.yakushev@uni-mainz.de
Dupont
Erwan
E
Buchholz
Hans-Georg
HG
Tillmanns
Julia
J
Debus
Fabian
F
Cumming
Paul
P
Heimann
Axel
A
Fellgiebel
Andreas
A
Luhmann
Heiko J
HJ
Landvogt
Christian
C
Werhahn
Konrad J
KJ
Schreckenberger
Mathias
M
Potschka
Heidrun
H
Bartenstein
Peter
P
D000818:Animals; D001345:Autoradiography / Q000706:statistics & numerical data; D001549:Benzamides / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008297:Male; D010862:Pilocarpine; D049268:Positron-Emission Tomography / Q000379:methods / Q000706:statistics & numerical data; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism
D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D010862:Pilocarpine; D004298:Dopamine