Effects of the kynurenine 3-hydroxylase inhibitor Ro 61-8048 after intrastriatal injections on the severity of dystonia in the dtsz mutant

Striatal dysfunctions seem to play a key role in the pathophysiology of dystonia in the dt(sz) mutant hamster, a model of paroxysmal non-kinesigenic dyskinesia, in which stress precipitates dystonic episodes. Previous examinations have shown changes in kynurenic acid levels and antidystonic effects of the kynurenine 3-hydroxylase inhibitor 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfon-amide (Ro 61-8048) after systemic treatment in dt(sz) hamsters. In the present study, intrastriatal injections of Ro 61-8048 (60-80 mu g/hemisphere) significantly reduced the severity of dystonia in dt(sz) hamsters, suggesting that kynurenine 3-hydroxylase inhibitors may be interesting candidates for managing dyskinesias which are related to striatal dysfunction. (C) 2008 Elsevier B.V. All rights reserved.