SEPTAL AND HIPPOCAMPAL GLUTAMATE RECEPTORS MODULATE THE OUTPUT OF ACETYLCHOLINE IN HIPPOCAMPUS - A MICRODIALYSIS STUDY

In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septu m/vertical limb of the diagonal band-(MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by usin g intracerebral microdialysis, Perfusion with N-methyl-D-aspartate (NM DA) and lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an increase in ACh output in the hippocampus. Th is increase was completely blocked by coadministration of their respec tive antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 6- cyano-7-nitroquinoxaline-2,3-dione (CNQX). Perfusion in the MS/vDB wit h kainic acid also caused an increase in ACh output. but coadministrat ion of CNQX attenuated the increase only partially. Perfusion with D-A P5 or CNQX alone in the septal probe did not affect ACh output from th e hippocampus. In contrast to the results of septal administration of NMDA and MPA, local perfusion with the same drugs in the hippocampus c aused a decrease in ACh output. Whereas the results of septal administ ration of drugs indicate that septal cholinergic neurons probably rece ive excitatory glutamatergic innervation, the decrease in ACh output c aused by administration of NMDA and AMPA in the hippocampus is poorly understood.