Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1068-73. doi: 10.1016/j.pnpbp.2011.03.002. Epub 2011 Mar 15.
Isolation-reared (IR) rats exhibit various cognitive and behavioral abnormalities in adulthood of which locomotor hyperactivity and impaired prepulse inhibition (PPI) of an acoustic startle reflex are the two cardinal characteristics. Using an amended social deprivation-resocialization paradigm, the present study examined the role of the developmental specificity of the effects of IR and its interaction with the non-competitive NMDA receptor antagonist, MK-801. Locomotor activity and PPI were measured in three groups of adult rats: social control, IR throughout life, and IR for the first two weeks after weaning followed by social housing. MK-801 was injected intraperitoneally (i.p.) 30 min prior to testing at doses of 0, 0.02, 0.1, and 0.2 mg/kg. The results revealed that locomotor activity increased only in rats in the IR throughout life group but not in the other two groups. The impairment of PPI was seen in rats in the IR for the first two weeks and the IR throughout life groups. Furthermore, the effect of MK-801 on PPI was bidirectional in rats of the IR for the first two weeks and IR throughout life groups but not in the social control group. These results suggest that the IR-induced behavioral effects are developed distinctively in terms of the critical period hypothesis, which strengthens the developmental hypothesis of schizophrenic-like dysfunctions.
隔离饲养（IR）的大鼠在成年后表现出各种认知和行为异常，其中运动过度和听觉惊跳反射的前脉冲抑制（PPI）受损是两个主要特征。本研究采用改良的社会剥夺-再社会化范式，探讨了 IR 效应的发展特异性及其与非竞争性 NMDA 受体拮抗剂 MK-801 的相互作用的作用。在三组成年大鼠中测量了运动活性和 PPI：社会对照组、终生 IR 组和断奶后前两周 IR 组，然后进行社交饲养。MK-801 在测试前 30 分钟通过腹腔注射（i.p.）给药，剂量为 0、0.02、0.1 和 0.2mg/kg。结果表明，仅在终生 IR 组的大鼠中观察到运动活性增加，而在其他两组中没有观察到。在第一至两周 IR 组和终生 IR 组的大鼠中观察到 PPI 受损。此外，MK-801 对 PPI 的影响在第一至两周 IR 组和终生 IR 组的大鼠中呈双向，但在社会对照组的大鼠中则没有。这些结果表明，IR 诱导的行为效应根据关键期假说具有独特的发展方式，这加强了精神分裂症样功能障碍的发育假说。
