Moor E, Auth F, DeBoer P, Westerink B H
Department of Medicinal Chemistry, University Centre for Pharmacy, Groningen, The Netherlands.
J Neurochem. 1996 Jul;67(1):310-6. doi: 10.1046/j.1471-4159.1996.67010310.x.
In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septum/vertical limb of the diagonal band (MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by using intracerebral microdialysis. Perfusion with N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an incrase in ACh output in the hippocampus. This increase was completely blocked by coadministration of their respective antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Perfusion in the MS/vDB with kainic acid also caused an increase in ACh output, but coadministration of CNQX attenuated the increase only partially. Perfusion with D-AP5 and CNQX alone in the septal probe did not affect ACh output from the hippocampus. In contrast to the results of septal administration of NMDA and AMPA, local perfusion with the same drugs in the hippocampus caused a decrease in ACh output. Whereas the results of septal administration of drugs indicate that septal cholinergic neurons probably receive excitatory glutamatergic innervation, the decrease in ACh output caused by administration of NMDA and AMPA in the hippocampus is poorly understood.
在本研究中，通过逆行微透析将谷氨酸受体激动剂和拮抗剂注入内侧隔区/斜角带垂直支（MS/vDB）或海马体，然后采用脑内微透析法测量海马体中乙酰胆碱（ACh）的释放量。在MS/vDB中灌注N-甲基-D-天冬氨酸（NMDA）和（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）可使海马体中ACh的释放量增加。分别同时给予其拮抗剂D-（-）-2-氨基-5-膦酰基戊酸（D-AP5）和6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）可完全阻断这种增加。在MS/vDB中灌注 kainic 酸也会导致ACh释放量增加，但同时给予CNQX只能部分减弱这种增加。单独在隔区探针中灌注D-AP5和CNQX不会影响海马体中ACh的释放。与在隔区给予NMDA和AMPA的结果相反，在海马体中局部灌注相同药物会导致ACh释放量减少。虽然在隔区给药的结果表明隔区胆碱能神经元可能接受兴奋性谷氨酸能神经支配，但对在海马体中给予NMDA和AMPA导致ACh释放量减少的情况了解甚少。
