Parelkar Nikhil K, Wang John Q
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
Neurosci Lett. 2008 Mar 15;433(3):250-4. doi: 10.1016/j.neulet.2008.01.015. Epub 2008 Jan 16.
Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors and are densely expressed in the forebrain of adult rats. Accumulative evidence suggests a critical role of mGluRs in the regulation of normal physiological activity of neurons and pathogenesis of mental illnesses such as schizophrenia, depression, and substance addiction. In this study, we investigated alterations in mGluR8 subtype mRNA expression in the rat forebrain in response to repeated intraperitoneal administration of amphetamine (twice daily for 12 days, 5mg/kg per injection) using quantitative in situ hybridization. We found that mGluR8 mRNA levels were profoundly increased in the dorsal (caudate putamen) and ventral (nucleus accumbens) striatum 1 day after the discontinuation of amphetamine treatments. Such increases were sustained up to 21 days of withdrawal. Increases in mGluR8 mRNAs were also found in the cerebral cortex, including the cingulate and sensory cortex but not the piriform cortex, at 1 and 21 days. These data demonstrate a positive response of mGluR8 in mRNA abundance in most forebrain regions to repeated stimulant exposure.
代谢型谷氨酸受体（mGluRs）是G蛋白偶联受体，在成年大鼠前脑中大量表达。越来越多的证据表明，mGluRs在调节神经元正常生理活动以及精神疾病（如精神分裂症、抑郁症和药物成瘾）的发病机制中起关键作用。在本研究中，我们使用定量原位杂交技术，研究了大鼠前脑中mGluR8亚型mRNA表达的变化，该变化是对反复腹腔注射苯丙胺（每天两次，共12天，每次注射5mg/kg）的反应。我们发现，在停止苯丙胺治疗1天后，背侧（尾状壳核）和腹侧（伏隔核）纹状体中的mGluR8 mRNA水平显著升高。这种升高在戒断长达21天的时间内持续存在。在第1天和第21天，在包括扣带回和感觉皮层但不包括梨状皮层的大脑皮层中也发现了mGluR8 mRNA的增加。这些数据表明，大多数前脑区域中mGluR8的mRNA丰度对反复刺激暴露有阳性反应。
