NMDA and non-NMDA ionotropic glutamate receptors modulate striatal acetylcholine release via pre- and postsynaptic mechanisms

The effects of NMDA and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on endogenous acetylcholine release from rat striatal slices and synaptosomes were investigated. Both agonists (1-300 μM) facilitated acetylcholine release from slices in a dose-dependent manner. NMDA (100-300 μM) and AMPA (30-300 μM), however, subsequently inhibited acetylcholine release. NMDA (100 μM)-induced facilitation was antagonized by 3-(2- carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and dizocilpine (both 1- 10 μM), whereas the 10 μM AMPA effect was antagonized by 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX; 1-30 μM). NMDA (100 μM)-induced inhibition was counteracted by CPP, but not dizocilpine, and by the nitric oxide synthase inhibitor L-nitroarginine (1-100 μM). Tetrodotoxin (0.5 μM) prevented the facilitatory effect of 3 μM NMDA and AMPA, but left unchanged that of 30 μM NMDA and 100 μM AMPA. Acetylcholine release from synaptosomes was stimulated by KCl (7.5-100 mM) in a dose-depend...