The metabotropic glutamate 5 (mGlu₅) receptor is critically involved in corticostriatal plasticity which is disturbed in various animal models of dystonia. Recently, the positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) exerted prodyskinetic effects in a phenotypic model of episodic dystonia. In the DYT1 knock-in (KI) mouse, a model for a persistent type of dystonia, previous ex vivo electrophysiological experiments indicated that mGlu₅ receptors are involved in abnormal striatal plasticity. Therefore, in the present study we examined the mGlu₅ receptor expression in the striatum and cortex of DYT1 KI mice in comparison with wildtype littermates. By immunohistochemistry (IHC) we found a lower expression of mGlu₅ receptors in the cortex (16%) and ventral striatum (10%) but not in the whole striatum of DYT1 KI mice, while mRNA levels were merely lower in the striatum of DYT1 KI mice (43%). However, mGlu₅ receptor protein levels measured by western blotting showed no significant differences in tissue of the whole striatum and in the cortex between both genotypes. Since DYT1 KI mice do not exhibit dystonic symptoms, we investigated if CDPPB provokes dystonia or dyskinesia. CDPPB (10, 20 and 30 mg/kg intraperitoneal, i.p.) did not induce abnormal movements and the locomotor activity did not differ between DYT1 KI and wildtype mice. The present data do not provide evidence for a crucial role of the mGlu₅ receptor in the pathophysiology of DYT1 dystonia, but corticostriatal changes are in line with the hypothesis of maladaptive plasticity in dystonia.

代谢型谷氨酸5（mGlu ₅）受体在皮质张力障碍的各种动物模型中都受到了极大的影响。最近，正变构调节剂3-氰基-N-（1,3-二苯基-1H-吡唑-5-基）苯甲酰胺（CDPPB）在间歇性肌张力障碍的表型模型中发挥促动力学作用。在DYT1敲入（KI）小鼠（一种持续性类型的肌张力障碍模型）中，先前的体外电生理实验表明，mGlu ₅受体参与异常的纹状体可塑性。因此，在本研究中，我们与野生型同窝仔相比，检查了DYT1 KI小鼠纹状体和皮质中mGlu ₅受体的表达。通过免疫组化（IHC），我们发现mGlu的表达较低在DYT1 KI小鼠的大脑皮层（16％）和腹侧纹状体（10％）中有_5种受体，但在整个纹状体中却没有，而在DYT1 KI小鼠的纹状体中有_5种受体，而mRNA含量较低（43％）。然而，通过蛋白质印迹法测量的mGlu ₅受体蛋白水平在两种基因型之间在整个纹状体组织和皮质中均无显着差异。由于DYT1 KI小鼠没有表现出肌张力障碍症状，因此我们研究了CDPPB是否引起肌张力障碍或运动障碍。CDPPB（10、20和30 mg / kg腹膜内，ip）不会引起异常运动，并且DYT1 KI和野生型小鼠的运动活性没有差异。目前的数据并未提供证据证明mGlu ₅的关键作用 受体在DYT1肌张力障碍的病理生理中起着重要作用，但是皮质口角变化与肌张力障碍中适应不良的可塑性假说相符。