Neonatal excitotoxic hippocampal damage in rats causes post pubertal changes in prepulse inhibition of startle and its disruption by apomorphine
Neonatal excitotoxic hippocampal damage in rats causes post pubertal changes in prepulse inhibition of startle and its disruption by apomorphine
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DOI：
10.1007/bf02246439
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发表时间：
1995-11-01
影响因子：
3.4
通讯作者：
Weinberger, DR
中科院分区：
文献类型：
--
作者：
Lipska, BK;Swerdlow, NR;Weinberger, DR
大鼠新生儿兴奋性毒性海马损伤导致青春期后出现与中边缘/黑质纹状体系统过度多巴胺能传递相关的各种异常行为;因此可以被认为是精神分裂症某些方面的动物模型。由于成年精神分裂症患者和实验诱导的中脑边缘多巴胺过度活跃的大鼠的感觉运动门控受损，因此本实验研究了新生儿（出生后第7天，PD 7）鹅膏蕈氨酸（3 μ g）腹侧海马（VH）损伤对青春期前（PD 35）和青春期后（PD 56）大鼠声惊吓的幅度和前脉冲抑制（PPI）的影响。惊吓引起单独使用105和118分贝脉冲或之前的4，8，或16分贝以上的背景前脉冲与车辆或阿扑吗啡（APO; 0.025或0.1毫克/千克SC）治疗的大鼠。在PD 35，在VH损伤大鼠的PPI没有显着差异，这些措施在假手术大鼠。阿扑吗啡显着增加惊吓幅度和减少PPI在假手术和VH-损伤大鼠在PD 35。在PD 56，VH损伤大鼠的惊吓幅度与对照组无显著差异，但PPI与对照组相比显著降低。APO治疗后，海马损伤大鼠的PPI也表现出过度降低。这些发现提供了进一步的证据，青春期后的损害，可能与增加中脑边缘多巴胺传输和受体敏感性的新生儿海马损伤的大鼠。并为精神分裂症动物模型的逼真性提供进一步支持。
Neonatal excitotoxic hippocampal damage in the rat results in postpubertal onset of a variety of abnormal behaviors related to excessive dopaminergic transmission in the mesolimbic/nigrostriatal system; and thus may be considered an animal model of some aspects of schizophrenia. Because sensorimotor gating is impaired in adult patients with schizophrenia and in rats with experimentally induced mesolimbic dopamine hyperactivity, the present experiments investigated the effects of neonatal (postnatal day 7, PD7) ibotenic acid (3 mu g) lesions of the ventral hippocampus (VH) on the amplitude and prepulse inhibition (PPI) of acoustic startle in prepubertal (PD35) and postpubertal (PD56) rats. Startle was elicited using 105 and 118-dB pulses alone or preceded by 4, 8, or 16 dB above-background prepulses in rats treated with vehicle or apomorphine (APO; 0.025 or 0.1 mg/kg SC). At PD35, PPI in VH-lesioned rats did not differ significantly from these measures in sham operated rats. Apomorphine significantly increased startle amplitude and reduced PPI in both sham operated and VH-lesioned rats at PD35. At PD56, startle amplitude in VH-lesioned rats was not significantly different from controls, but PPI was reduced significantly compared to controls. Ventral hippocampus lesioned rats also exhibited an exaggerated reduction in PPI after treatment with APO. These findings provide further evidence of postpubertal impairments that may be related to increased mesolimbic dopamine transmission and receptor sensitivity in rats with neonatal hippocampal damage. and provide further support for the fidelity of this animal model of schizophrenia.