Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment
Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment
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DOI：
10.1038/sj.npp.1300468
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发表时间：
2004-09-01
影响因子：
7.6
通讯作者：
Ressler, KJ
中科院分区：
文献类型：
--
作者：
Heldt, SA;Green, A;Ressler, KJ
最近的人类尸检研究表明，GABA 能神经传递缺陷可能导致与精神分裂症相关的神经病理学。 GABA 能系统的紊乱也可能导致精神分裂症患者中经典观察到的感觉运动门控缺陷，包括前脉冲抑制 (PPI) 缺陷。为了探索这种关系，当前的研究检查了缺乏 GABA 合成酶谷氨酸脱羧酶 65 (GAD 65) 的基因敲除 (KO) 小鼠中 PPI 和惊吓习惯的完整性。 GAD65 KO 小鼠表现出正常的基线和习惯性惊吓反应，这与 GAD65 野生型 (WT) 或杂合型 (HET) 小鼠没有差异。然而，GAD65 KO 小鼠表现出 PPI 的严重缺陷，这种缺陷可以被非典型抗精神病药物氯氮平逆转。这些结果支持了这样的观点：GABA 能系统的异常可能有助于精神分裂症的基本病理生理机制。
Recent postmortem studies in humans suggest that defects in GABAergic neurotransmission might contribute to the neuropathology associated with schizophrenia. Disturbances in GABAergic systems may also contribute to the sensorimotor gating deficits classically observed in schizophrenic patients, including deficits in prepulse inhibition (PPI). To explore the relationship, the current study examined the integrity of PPI and startle habituation in knockout ( KO) mice that lack the GABA synthesizing enzyme glutamic acid decarboxylase 65 (GAD 65). GAD65 KO mice displayed normal baseline and habituated startle responses, which did not differ from GAD65 wild-type (WT) or heterozygous ( HET) mice. However, GAD65 KO mice showed robust deficits in PPI which were reversed by the atypical antipsychotic agent clozapine. These results lend support to the view that abnormalities in GABAergic systems might contribute to the basic pathophysiological mechanisms in schizophrenia.