In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy

Authors: Yakushev, Igor Y.; Dupont, Erwan; Buchholz, Hans-Georg¹; Tillmanns, Julia¹; Debus, Fabian²; Cumming, Paul³; Heimann, Axel⁴; Fellgiebel, Andreas²; Luhmann, Heiko J.⁵; Landvogt, Christian¹; Werhahn, Konrad J.⁶; Schreckenberger, Mathias¹; Potschka, Heidrun⁷; Bartenstein, Peter

Source: Epilepsia, Volume 51, Number 3, March 2010 , pp. 415-422(8)

Publisher: Wiley-Blackwell

Abstract:

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 [¹⁸F]-fallypride, a high-affinity dopamine D_2/3 receptor ligand. Parametric images of [¹⁸F]-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.

Keywords: Pilocarpine model; Positron emission tomography; Animal PET; Dopamine; D2/3 receptors; Fallypride

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2009.02272.x

Affiliations: 1: Department of Nuclear Medicine, University of Mainz, Mainz, Germany 2: Department of Psychiatry, University of Mainz, Mainz, Germany 3: Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany 4: Institute for Neurosurgical Pathophysiology, University of Mainz, Mainz, Germany 5: Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany 6: Department of Neurology, University of Mainz, Mainz, Germany 7: Institute of Pharmacology, Toxicology and Pharmacy, University of Munich (LMU), Munich, Germany

Publication date: 2010-03-01

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• In this Subject: Neurology & Psychiatry
• By this author: Yakushev, Igor Y. ;  Dupont, Erwan ;  Buchholz, Hans-Georg ;  Tillmanns, Julia ;  Debus, Fabian ;  Cumming, Paul ;  Heimann, Axel ;  Fellgiebel, Andreas ;  Luhmann, Heiko J. ;  Landvogt, Christian ;  Werhahn, Konrad J. ;  Schreckenberger, Mathias ;  Potschka, Heidrun ;  Bartenstein, Peter

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