Disruption of prepulse inhibition in mice lacking mGluR1
Disruption of prepulse inhibition in mice lacking mGluR1
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DOI：
10.1111/j.1460-9568.2003.03073.x
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发表时间：
2003-12-01
影响因子：
3.4
通讯作者：
Geyer, MA
中科院分区：
文献类型：
--
作者：
Brody, SA;Conquet, F;Geyer, MA
感觉运动门控是通过惊吓反应（PPI）的前脉冲抑制来测量的，是一种跨物种的信息处理形式，在精神分裂症患者中存在缺陷，并且被广泛用作研究这种疾病的神经生物学的模型。八种已知的代谢型谷氨酸受体 (mGluR) 根据序列同源性和药理学特性分为三组。 I 组由 mGluR5 和 mGluR1 组成，两者均与磷脂酶 C 呈正偶联。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 敲除 (KO) 小鼠的 PPI。同窝 mGluR1 野生型和 KO 小鼠在多个年龄的标准 PPI 范例中进行了测试，其中包含 65 dB 背景、120 dB 脉冲和 69、73 和 77 dB 前脉冲。在所有测试年龄阶段，mGluR1 KO 小鼠均表现出显着的 PPI 缺陷。 mGluR1 KO 小鼠的 PPI 缺陷并未因给予 N-甲基-D-天冬氨酸拮抗剂苯环利定而进一步加剧，也不会因给予多巴胺拮抗剂雷氯必利（3.0 mg/kg）而逆转。然而，mGluR1 KO 小鼠的 PPI 缺陷可通过服用情绪稳定剂拉莫三嗪（27 mg/kg 基础当量体重）得到改善，尽管在野生型小鼠中使用拉莫三嗪也发现 PPI 增加。因此，I 组代谢型谷氨酸受体均参与小鼠 PPI 的调节。
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.