Non-NMDA glutamatergic receptors modulate acetylcholine release in the rat subfornical organ area

The present study was designed to examine whether glutamatergic receptor mechanisms modulate the release of acetylcholine (ACh) in the region of the subfornical organ (SFO) using intracerebral microdialysis methods in freely moving rats. Perfusion of either non-N-methyl-d-aspartate (NMDA) agonist quisqualic acid (QA, 50 μM) or kainic acid (KA, 50 μM) through the microdialysis probe significantly enhanced the ACh release in the SFO area. Local perfusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 and 50 μM) did not change the basal release of ACh. CNQX (10 μM) administered together with either QA (50 μM) or KA (50 μM) in the SFO area antagonized the stimulant effect of the agonists on the ACh release. In urethane-anesthetized rats, repetitive electrical stimulation (500 μA, 10 Hz) of the medial septum (MS) significantly increased dialysate ACh concentrations in the region of the SFO. The increase in the ACh release elicited by the MS stimulation was significantly potentiated by perfusion of QA (50 μM), and the QA-induced potentiation was prevented by CNQX (10 μM) treated together with QA. These results show that the glutamatergic synaptic inputs enhance the ACh release in the SFO area through non-NMDA receptors. The data further suggest that the septal cholinergic inputs to the SFO area are potentiated by non-NMDA receptor mechanisms.