Modulation of striatal acetylcholine concentrations by NMDA and the competitive NMDA receptor-antagonist AP-5: an in vivo microdialysis study

The effects of local perfusion with the competitive NMDA receptor antagonis t 2-amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-m ethyl-D-aspartate (NMDA) on release of extracellular acetylcholine (ACh) an d choline (Ch) in the dorsolateral striatum were studied using in vivo micr odialysis in freely moving rats. AP-5 caused a dose-dependent decrease in A Ch release that was counteracted by the addition of NMDA. Perfusion with AP -5 also decreased Ch levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(-5) M), but not high (10(-2) M and 10(-3) M) con centrations, that were associated with massive cellular death. These inhibi tory effects of AP-5 and the stimulatory effect-of NMDA in non-neurotoxic d osages on ACh release provide further evidence for a tonic stimulation of s triatal cholinergic interneurons by glutamatergic neurons via NMDA receptor s.