Kato K, Shishido T, Ono M, Shishido K, Kobayashi M, Suzuki H, Nabeshima T, Furukawa H, Niwa S
Department of Neuropsychiatry, Fukushima Medical University, School of Medicine, Fukushima City, Japan.
Psychopharmacology (Berl). 2000 Jun;150(2):163-9. doi: 10.1007/s002130000433.
The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia.
To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat.
In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method.
Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats.
The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.
在精神分裂症动物模型中，使用新生海马损伤大鼠已得到充分证实。此外，N-甲基-D-天冬氨酸（NMDA）神经传递功能障碍可能在精神分裂症的病理生理学中起关键作用。
研究NMDA神经传递在新生腹侧海马损伤大鼠中的作用。
在初始实验中，我们比较了轻度环境应激（HAB）以及向损伤大鼠和假手术大鼠注射生理盐水和甲基苯丙胺（MAP，1.5mg/kg，腹腔注射）的效果。我们还使用体内脑微透析方法，研究了向损伤大鼠和假手术大鼠单次注射苯环利定（PCP，10mg/kg，腹腔注射）对其运动活性以及伏隔核（NAc）中多巴胺（DA）及其代谢产物细胞外水平的影响。
与假手术对照组相比，损伤大鼠在接受HAB和MAP处理后，于出生后第56天（PD56）表现出运动活性增加，但在PD35时未出现此现象。同样，损伤大鼠在接受PCP处理后，于PD56表现出运动活性增加，但在PD35时未出现。出乎意料的是，假手术大鼠中DA水平的增加显著大于损伤大鼠。
结果表明，新生海马损伤大鼠伴有NMDA神经传递功能障碍。它们还表明，新生海马损伤后对PCP的高反应性并不取决于NAc中的细胞外DA浓度。
