Belfiore P, Ponzio F, Biagetti R, Berettera C, Magnani M, Pozzi O
ISF-Laboratories for Biomedical Research, Trezzano s/N, Milan, Italy.
Neurosci Lett. 1992 Aug 31;143(1-2):127-30. doi: 10.1016/0304-3940(92)90248-6.
The intracerebroventricular injection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-7-phosphonoheptanoic acid (AP7) induces an increase of the hippocampal levels of acetylcholine (ACh) which is dose-dependent in the range 1.5-10 micrograms. Similar doses of AP7 failed to affect the ACh content of the striatum. The effect of the i.c.v. administration of 3.5 micrograms AP7 on hippocampal ACh levels was prevented by pretreatment with oxiracetam 100 mg/kg i.p. In the passive avoidance test the i.c.v. administration of 3.5 micrograms of AP7 caused severe amnesia which was antagonized in a dose-dependent manner by the pretreatment with oxiracetam. These results show that oxiracetam prevents the imbalance of cholinergic activity and the amnesia caused by blockade of NMDA receptors. The present study suggests that the hippocampal cholinergic activity is modulated by glutamatergic neuronal pathways and that the functional integrity of both systems is essential for learning and memory processes.
脑室内注射N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D，L-2-氨基-7-磷酸庚酸（AP7）可使海马中乙酰胆碱（ACh）水平升高，在1.5至10微克范围内呈剂量依赖性。相似剂量的AP7未能影响纹状体中的ACh含量。腹腔注射100mg/kg奥拉西坦预处理可阻止脑室内注射3.5微克AP7对海马ACh水平的影响。在被动回避试验中，脑室内注射3.5微克AP7可导致严重失忆，而奥拉西坦预处理可呈剂量依赖性地拮抗这种失忆。这些结果表明，奥拉西坦可预防胆碱能活性失衡以及由NMDA受体阻断引起的失忆。本研究提示，海马胆碱能活性受谷氨酸能神经元通路调节，且这两个系统的功能完整性对于学习和记忆过程至关重要。
