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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effect of a prolyl endopeptidase inhibitor, JTP-4819, on radial maze performance in hippocampal-lesioned rats.
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Effect of a prolyl endopeptidase inhibitor, JTP-4819, on radial maze performance in hippocampal-lesioned rats.

机译：脯氨酰内肽酶抑制剂JTP-4819对海马损伤大鼠radial骨迷宫性能的影响。

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摘要

The effect of a novel prolyl endopeptidase (PEP) inhibitor, (S)-2-2[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl) -1-pyrrolidinecarboxamide (JTP-4819), on spatial learning deficits in rats with dorsal hippocampal (DH) lesions was examined using an eight-arm radial maze. The correct performance remained at chance levels even after 18 acquisition trials in rats with DH lesions. JTP-4819 (3.0 mg/kg, p.o.) significantly ameliorated this learning impairment after 34-41 days of treatment. When DH lesions were created in rats after achievement of learning, postoperative performance deteriorated prominently, but gradually recovered with the repetition of trials. JTP-4819 (3.0 mg/kg, p.o.) significantly decreased the number of trials needed to reattain learning criterion. After the behavioral experiment, the choline acetyltransferase (ChAT) activity and [3H]-pirenzepine binding (Kd, Bmax) in the residual hippocampus and cerebral cortex were analyzed. Neither parameter was significantly affected by JTP-4819. In conclusion, JTP-4819 can improve both learning and relearning deficits of spatial memory in DH-lesioned rats, postulating that enhancement of neuropeptide activity via PEP inhibition may be involved in the mechanism of action of JTP-4819.
机译：新型脯氨酰内肽酶（PEP）抑制剂（S）-2-2 [[（（S）-2-（羟乙酰基）-1-吡咯烷基]羰基] -N-（苯甲基）-1-吡咯烷甲酰胺（JTP- 4819），使用八臂放射状迷宫检查背海马（DH）损伤大鼠的空间学习缺陷。即使在有DH损伤的大鼠进行18次获得性试验后，正确的表现仍保持在偶然的水平。在治疗34-41天后，JTP-4819（3.0 mg / kg，p.o.）明显改善了这种学习障碍。学习完成后在大鼠体内产生DH损伤时，术后表现显着下降，但随着试验的重复逐渐恢复。 JTP-4819（3.0 mg / kg，p.o.）大大减少了重新达到学习标准所需的试验次数。进行行为实验后，分析了残留海马和大脑皮层中的胆碱乙酰基转移酶（ChAT）活性和[3H]-哌仑西平结合（Kd，Bmax）。这两个参数均不受JTP-4819的明显影响。综上所述，JTP-4819可以改善DH损伤大鼠的学习记忆能力和再学习空间记忆障碍，并假定通过PEP抑制增强神经肽活性可能与JTP-4819的作用机制有关。

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