Abe E, Murai S, Saito H, Masuda Y, Takasu Y, Shiotani T, Tachizawa H, Itoh T
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
J Neural Transm Gen Sect. 1994;95(3):179-93. doi: 10.1007/BF01271565.
The effects of nefiracetam [DM-9384; N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide] and of phosphatidylcholine on a step-up active avoidance response, locomotor activities and regional brain cholinergic and monoaminergic neurotransmitters in AF64A-treated mice were investigated. Intracerebroventricular (i.c.v.) injection of AF64A (ethylcholine mustard aziridinium ion; 8 nmol/ventricle) impaired acquisition and retention of the avoidance task, and increased vertical and horizontal locomotor activities. Regional levels of acetylcholine, noradrenaline, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased and homovanillic acid (HVA) levels were increased in the hippocampus but not in the septum, cerebral cortex or striatum of AF64A-treated animals. Administration of nefiracetam (3 mg/kg, p.o.) twice daily for 9 days to AF64A-treated animals ameliorated the deficit in active avoidance response in addition to attenuating the increase in locomotor activities. In parallel with these behavioural effects, nefiracetam reversed AF64A-induced alterations in the hippocampal profiles of cholinergic and monoaminergic neurotransmitters and their metabolites. In contrast, administration of phosphatidylcholine (30 mg/kg, p.o.) twice daily for 9 days had no significant effect on the deficit in active avoidance response, despite significantly reversing the decrease in acetylcholine levels in the hippocampus. These results indicate that the effects of nefiracetam on AF64A-induced behavioural deficits are probably due to its ability to facilitate both cholinergic and monoaminergic neurotransmitter systems.
研究了奈非西坦[DM - 9384；N-(2,6 - 二甲基苯基)-2-(2 - 氧代吡咯烷基)乙酰胺]和磷脂酰胆碱对经AF64A处理的小鼠的逐步主动回避反应、运动活动以及脑区胆碱能和单胺能神经递质的影响。脑室内(i.c.v.)注射AF64A(乙基胆碱氮芥吖丙啶离子；8 nmol/脑室)损害了回避任务的习得和保持，并增加了垂直和水平运动活动。在经AF64A处理的动物的海马中，乙酰胆碱、去甲肾上腺素、3 - 甲氧基 - 4 - 羟基苯乙二醇(MHPG)、5 - 羟色胺(5 - HT)和5 - 羟吲哚乙酸(5 - HIAA)的区域水平显著降低，高香草酸(HVA)水平升高，但在隔区、大脑皮层或纹状体中未出现这种情况。对经AF64A处理的动物每天口服两次奈非西坦(3 mg/kg)，持续9天，除了减轻运动活动增加外，还改善了主动回避反应的缺陷。与这些行为效应同时，奈非西坦逆转了AF64A诱导的海马胆碱能和单胺能神经递质及其代谢产物谱的改变。相比之下，每天口服两次磷脂酰胆碱(30 mg/kg)，持续9天，尽管显著逆转了海马中乙酰胆碱水平的降低，但对主动回避反应的缺陷没有显著影响。这些结果表明，奈非西坦对AF64A诱导的行为缺陷的影响可能归因于其促进胆碱能和单胺能神经递质系统的能力。
