Activation of non-NMDA receptors stimulates acethylcholine and GABA release from dorsal hippocampus: a microdialysis study in the rat

The effect of the non-N-methyl-D-aspartate (NMDA) agonists (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and quisqualate (QUIS) on the release of acetylcholine (ACh), g-amino butyric acid (GABA), aspartate (Asp) and glutamate (Glu) from the hippocampus of freely moving rats was studied by transversal microdialysis. Intracerebroventricular (i.c.v.) administration of the non-NMDA receptor agonist AMPA (0.5 nmol) enhanced (by about 200%) ACh release from the hippocampus. The effect of AMPA was completely antagonized by 6-nitro-7-sulphamoyl-benz(f)quinoxaline-2,3-dione (NBQX; 2 nmol, i.c.v). No effect was seen when AMPA was perfused through the septum. However, AMPA (200 mM) locally applied to the hippocampus, increased (by about 200%) ACh release. QUIS (200 mM) applied locally to the hippocampus produced a longlasting increase in the release of ACh (by about 215%) and GABA (by about 460%). Local infusion of tetrodotoxin (1 mM) decreased ACh and GABA basal extracellular levels, and abolished the QUIS-induced increase in ACh and GABA. Our results demonstrate that non-NMDA glutamatergic receptors in the hippocampus regulate hippocampal release of GABA and ACh.