Brody S A, Conquet F, Geyer M A
Department of Psychiatry and Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA.
Eur J Neurosci. 2003 Dec;18(12):3361-6. doi: 10.1111/j.1460-9568.2003.03073.x.
Sensorimotor gating, measured by prepulse inhibition of the startle response (PPI), is a cross-species form of information processing that is deficient in patients with schizophrenia and is widely used as a model to study the neurobiology of this disorder. The eight known metabotropic glutamate receptors (mGluRs) are divided into three groups on the basis of sequence homology and pharmacological properties. Group I consists of mGluR5 and mGluR1, both of which are coupled positively to phospholipase C. Mice lacking mGluR5 exhibit a deficit in PPI. Like mGluR5, mGluR1 is located in regions that are involved in the modulation of PPI. To test the hypothesis that mGluR1 is involved in the modulation of PPI we assessed PPI in mGluR1 knockout (KO) mice. Littermate mGluR1 wild-type and KO mice were tested at multiple ages in a standard PPI paradigm containing a 65 dB background, 120 dB pulses and prepulses of 69, 73 and 77 dB. At all ages tested, mGluR1 KO mice exhibited a significant PPI deficit. The PPI deficit of the mGluR1 KO mice was not further exaggerated by administration of the N-methyl-d-aspartate antagonist phencyclidine nor was it reversed by administration of the dopamine antagonist raclopride (3.0 mg/kg). The PPI deficit of the mGluR1 KO mice was, however, ameliorated by administration of the mood stabilizer lamotrigine (27 mg/kg base equivalent weight), though increases in PPI were also seen with lamotrigine in the wild-type mice. Thus, both group I metabotropic glutamate receptors are involved in the regulation of PPI in mice.
感觉运动门控通过惊吓反应的前脉冲抑制（PPI）来测量，是一种跨物种的信息处理形式，精神分裂症患者存在这种缺陷，它被广泛用作研究该疾病神经生物学的模型。已知的8种代谢型谷氨酸受体（mGluRs）根据序列同源性和药理学特性分为三组。第一组包括mGluR5和mGluR1，两者均正向偶联至磷脂酶C。缺乏mGluR5的小鼠表现出PPI缺陷。与mGluR5一样，mGluR1也位于参与PPI调节的区域。为了验证mGluR1参与PPI调节的假设，我们评估了mGluR1基因敲除（KO）小鼠的PPI。同窝出生的mGluR1野生型和KO小鼠在多个年龄段，在包含65 dB背景、120 dB脉冲以及69、73和77 dB前脉冲的标准PPI范式中进行测试。在所有测试的年龄段，mGluR1 KO小鼠均表现出明显的PPI缺陷。给予N-甲基-D-天冬氨酸拮抗剂苯环利定并未进一步加重mGluR1 KO小鼠的PPI缺陷，给予多巴胺拮抗剂雷氯必利（3.0 mg/kg）也未使其逆转。然而，给予情绪稳定剂拉莫三嗪（27 mg/kg碱基当量）可改善mGluR1 KO小鼠的PPI缺陷，不过野生型小鼠使用拉莫三嗪后PPI也有所增加。因此，第一组代谢型谷氨酸受体均参与小鼠PPI的调节。
