Kaatz K W, Albin R L
Department of Neurology, University of Michigan, Ann Arbor 48109, USA.
Neuroscience. 1995 May;66(1):55-65. doi: 10.1016/0306-4522(94)00568-p.
Prior work has shown that intrastriatal injection of the metabotropic glutamate receptor agonist 1S,3R-ACPD results in pronounced contralateral rotation, and the basis for this effect is thought to be increased activity of dopaminergic nigrostriatal neurons. We tested this hypothesis by determining the expression of Fos-like immunoreactivity after intrastriatal injection of 1S,3R-ACPD. Intense Fos-like immunoreactivity was noted in the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata. Ablation of the subthalamic nucleus 10 days prior to intrastriatal injection of 1S,3R-ACPD abolished rotational behaviour but not Fos-like immunoreactivity in the globus pallidus, entopeduncular nucleus and substantia nigra. Intrasubthalamic injection of 1S,3R-ACPD produced marked contralateral rotation and a pattern of Fos-like immunoreactivity similar to that seen after intrastriatal 1S,3R-ACPD injection. These results suggest that stimulation of striatal metabotropic glutamate receptors inhibits striatal projection neuron activity, while stimulation of subthalamic metabotropic glutamate receptors increases subthalamic nucleus activity. Increased subthalamic nucleus activity is necessary and sufficient for the expression of rotational behavior. These results also suggest that metabotropic glutamate receptor antagonists may be useful in the treatment of Parkinson's disease.
先前的研究表明，向纹状体内注射代谢型谷氨酸受体激动剂1S,3R-ACPD会导致明显的对侧旋转，这种效应的基础被认为是多巴胺能黑质纹状体神经元的活性增加。我们通过测定纹状体内注射1S,3R-ACPD后Fos样免疫反应性的表达来验证这一假设。在苍白球、内苍白球核、丘脑底核和黑质网状部观察到强烈的Fos样免疫反应性。在纹状体内注射1S,3R-ACPD前10天损毁丘脑底核，可消除旋转行为，但苍白球、内苍白球核和黑质中的Fos样免疫反应性不受影响。向丘脑底核内注射1S,3R-ACPD可产生明显的对侧旋转，且Fos样免疫反应性模式与纹状体内注射1S,3R-ACPD后相似。这些结果表明，刺激纹状体代谢型谷氨酸受体会抑制纹状体投射神经元的活性，而刺激丘脑底核代谢型谷氨酸受体会增加丘脑底核的活性。丘脑底核活性增加对于旋转行为的表达是必要且充分的。这些结果还表明，代谢型谷氨酸受体拮抗剂可能对帕金森病的治疗有用。
