Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats
Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats
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DOI：
10.1007/s00213-009-1527-2
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
T. Uehara;T. Sumiyoshi;T. Seo;H. Itoh;T. Matsuoka;Michio Suzuki;M. Kurachi
中科院分区：
文献类型：
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作者：
T. Uehara;T. Sumiyoshi;T. Seo;H. Itoh;T. Matsuoka;Michio Suzuki;M. Kurachi
N-甲基-D-天冬氨酸(NMDA)受体的合理阻断已被证明能在啮齿动物和人类身上产生一些与精神分裂症症状有关的异常行为。NMDA受体阻滞剂MK-801(0.13 mg/kg或0.20 mg/kg)对成年大鼠造成感觉运动门控缺陷。动物在青春期前(PD 35-38)和青春期后(PD 56-59)进行两次脉冲抑制(PPI)和运动活动测试。结果新生儿暴露于两种剂量的MK-801破坏了青春期和成年期早期的PPI。低剂量的MK-801对惊吓幅度有长期影响，而高剂量的MK-801则没有。两种剂量的MK-801对小鼠的自发活动均无明显影响，而高剂量的MK-801可使自发活动减弱。结论本研究结果提示，MK-801对青春期和成年期早期的感觉运动门控有干扰作用。这些结果表明，新生期间短暂暴露于NMDA阻滞剂的大鼠对精神分裂症的病理生理研究和治疗是有用的。
RationaleBlockade ofN-methyl-d-asparate (NMDA) receptors has been shown to produce some of the abnormal behaviors related to symptoms of schizophrenia in rodents and human. Neonatal treatment of rats with non-competitive NMDA antagonists has been shown to induce behavioral abnormality in a later period.ObjectivesThe aim of this study was to determine whether brief disruption of NMDA receptor function during a critical stage of development is sufficient to produce sensorimotor-gating deficits in the late adolescence or early adulthood in the rat.MethodsMale pups received the NMDA receptor blocker MK-801 (0.13 or 0.20 mg/kg), or an equal volume of saline on postnatal day (PD) 7 through 10. The animals were tested twice for prepulse inhibition (PPI) and locomotor activity in pre- (PD 35-38) and post- (PD 56-59) puberty.ResultsNeonatal exposure to both doses MK-801 disrupted PPI in the adolescence and early adulthood. Low-dose MK-801 elicited long-term effects on startle amplitudes, whereas high-dose MK-801 did not. Neither dose of MK-801 showed a significant effect on spontaneous locomotor activity, whereas the high dose attenuated rearing.ConclusionsThe results of this study suggest neonatal exposure to MK-801 disrupted sensorimotor gating in the adolescence and early adulthood stages. These findings indicate that rats transiently exposed to NMDA blockers in neonatal periods are useful for the study of the pathophysiology and treatment of schizophrenia.